Nkhani

Javascript ndiyoyimitsidwa pa msakatuli wanu pano.Zina za tsambali sizigwira ntchito ngati JavaScript yayimitsidwa.
Lembetsani ndi tsatanetsatane wanu komanso mankhwala omwe mukufuna, ndipo tidzafanana ndi zomwe mumapereka ndi zolemba zomwe zili munkhokwe yathu yayikulu ndikutumizirani kopi ya PDF nthawi yomweyo.
Ding Jingnuo, Zhao Weifeng, Dipatimenti ya Matenda opatsirana, Suzhou University First Affiliated Hospital, Suzhou City, Province la Jiangsu, 215000 Tel.zotupa za m'mimba dongosolo ndi 5 zaka zonse kupulumuka 14.1%.Odwala ambiri omwe ali ndi HCC amapezeka kuti ali pachiwopsezo, motero kuyezetsa msanga ndikofunikira kuti muchepetse kufa ndi HCC.Kuphatikiza pa zizindikiro zomwe zimagwiritsidwa ntchito nthawi zambiri monga serum alpha-fetoprotein (AFP), lens lectin-reactive alpha-fetoprotein (AFP-L3), ndi abnormal prothrombin (vitamin K deficiency-induced protein II, PIVKA-II), njira zamadzimadzi za biopsy. Zasonyezedwa kuti ndizopindulitsa pakuzindikiritsa HCC.Poyerekeza ndi njira zowononga, biopsy yamadzimadzi imatha kuzindikira ma metabolites oyipa omwe akuzungulira.Njira zamadzimadzi zamadzimadzi zimazindikira ma cell chotupa ozungulira, chotupa cha DNA, kuzungulira kwa RNA, ndi ma exosomes ndipo amagwiritsidwa ntchito powunika koyambirira, kuzindikira, komanso kuwunika bwino kwa HCC.Nkhaniyi ikuwunikiranso zasayansi yamamolekyulu komanso kugwiritsa ntchito njira zosiyanasiyana zamadzimadzi zamadzimadzi kuti azitha kusiyanitsa zolonjezedwa zomwe zitha kukhala zothandiza pakuwunika koyambirira kwa HCC kuti athandizire kuwunika koyambirira kwa magulu omwe ali pachiwopsezo chachikulu cha HCC.Mawu osakira: njira yamadzimadzi ya biopsy, hepatocellular carcinoma, gulu lowopsa kwambiri.
Hepatocellular carcinoma (HCC) ndi chotupa choopsa chofala m'mimba, chomwe chili pa nambala 6 pa milandu yatsopano ya zotupa zowopsa mwa amuna ndi akazi.1 Padziko lonse lapansi, khansa ya chiwindi ndi yachitatu yomwe imayambitsa kufa kwa khansa pambuyo pa khansa ya m'mapapo ndi khansa yapakhungu, yomwe imawerengera 8.3% yaimfa zokhudzana ndi khansa kuchokera ku ma neoplasms onse oyipa.1 Kudziwikiratu kwa HCC kumagwirizana kwambiri ndi nthawi yopezeka.Zifukwa zazikulu za kupulumuka osauka mu HCC ndi intrahepatic metastases, portal venous chotupa thrombi, ndi metastases kutali precluding resection, ndipo zambiri mwa makhalidwe amenewa alipo kale odwala pa nthawi ya matenda.
Kutengera ndi malangizo owunikira komanso chithandizo chamankhwala, zomwe zimayambitsa chiopsezo chachikulu cha HCC ndi matenda enaake a chiwindi, matenda a hepatitis B (HBV) kapena matenda a hepatitis C (HCV), matenda a chiwindi chamafuta oledzeretsa, komanso matenda a chiwindi amafuta osamwa mowa (NAFLD). ).2 Kuphatikiza apo, zinthu zowopsa za HCC zimaphatikizapo kudya zakudya zokhala ndi poizoni wa aflatoxin, likodzo, zomwe zimayambitsa matenda a cirrhosis, mbiri yabanja ya khansa ya chiwindi, matenda a shuga, kunenepa kwambiri, kusuta, ndi kuvulala kwachiwindi chifukwa cha mankhwala.Magulu azaka zapakati pa 35 ndi 45 omwe ali pachiwopsezo chachikulu amayenera kukayezetsa magazi pafupipafupi.Kuwunika koyambirira ndi njira yofunika kwambiri yothandizira odwala omwe ali ndi HCC kuti akhale ndi moyo wabwino.
Ma biomarkers monga AFP, AFP-L3 ndi PIVKA-II amalangizidwa kuti awonetsere msanga HCC3,4.Njira zama biopsy zamadzimadzi zawonetsa zotsatira zabwino pakuzindikira koyambirira komanso kuwunika kwamankhwala.5,6 Kupita patsogolo kwakukulu kwapangidwa mu HCC fluid biopsy, yomwe ingakhale ndi chidziwitso chapamwamba komanso chodziwika bwino kuposa zolembera za seramu zomwe zimagwiritsidwa ntchito kawirikawiri monga AFP (Table 1).
AFP ndi biomarker yomwe imagwiritsidwa ntchito kwambiri ku HCC ndipo pakadali pano ndiyo chizindikiro chatsatanetsatane chomwe chimagwiritsidwa ntchito kwambiri powunika msanga, kuzindikira, ndikuwunika matendawa.Kuchulukirachulukira kwa AFP kumawonedwa ngati chinthu chowopsa pakukula kwa HCC.7,8 Kuzindikira kwa kansalu kakang'ono ka hepatocellular carcinoma (sHCC) ikuwonjezeka ndi chitukuko cha ultrasound ndi computed tomography, ndipo AFP yapezeka kuti imakhala yosakhudzidwa kwambiri ndi kudziwika kwa hHCC muzochitika zachipatala.Malinga ndi kafukufuku wobwereza wa multicentre9, AFP positive idapezeka mu 46% (616/1338) ya milandu ya HCC ndi 23.4% (150/641) ya milandu ya sHCC.Kuphatikiza apo, milingo ya AFP imakwezedwa mwa odwala omwe ali ndi matenda a chiwindi ndi matenda a cirrhosis.10 Chifukwa chake, AFP ili ndi zotsatira zochepa zowonera sHCC.11 Malingana ndi Asia-Pacific Clinical Practice Guidelines for Hepatocellular Carcinoma, kugwiritsa ntchito AFP sikuvomerezeka.12 Umboni wachipatala umasonyeza kuti PIVKA-II ndi yapamwamba kuposa AFP pochiza HCC komanso kuti kuphatikiza kwa PIVKA-II ndi AFP kuli mtengo wapamwamba wowunikira mu HCC.13 Poyerekeza ndi biopsy ya minofu, biopsy yamadzimadzi imazindikira ma metabolites okhudzana ndi chotupa m'madzi am'thupi (mwazi, malovu, pleural fluid, cerebrospinal fluid, kapena mkodzo) ndipo sasokoneza kwambiri minofu.14 Kuphatikiza apo, ma biopsies amadzimadzi amatha kuwonetsa zowopsa zomwe sizipezeka m'minofu yayikulu yotupa.15 Ma biopsies amadzimadzi sanayesedwebe m'machitidwe azachipatala amitundu yonse ya zotupa, koma kuthekera kwawo kozindikira khansa kumakopa chidwi cha akatswiri a oncologist.16 Fluid biopsy imatha kuzindikira ma cell chotupa (CTCs), DNA chotupa (cDNA), RNA yaulere (ecRNA), ndi exosomes.M'nkhaniyi, tikambirana za mawonekedwe, udindo, ndi kugwiritsa ntchito njira zosiyanasiyana zamadzimadzi zamadzimadzi pakuwunika koyambirira kwa magulu omwe ali pachiwopsezo chachikulu cha HCC.
DNA ya extracellular (cfDNA) m'magazi a anthu athanzi idafotokozedwa koyamba mu 1948 ndi Mandel et al.17 cfDNA ndi chidutswa cha DNA chopanda maselo pafupifupi 160-180 bp m'litali, chochokera ku ma lymphocyte ndi ma cell a myeloid.ctDNA ndi gawo linalake la DNA losasinthika lomwe limatulutsidwa ndi maselo otupa m'magazi ozungulira, omwe amayimira chidziwitso chamtundu wa maselo otupa pambuyo pa njira zina za pathophysiological, kuphatikiza necrosis, apoptosis, ndi excretion.Kuchuluka kwa ctDNA mu cfDNA yonse kumasiyana mosiyanasiyana ndi mtundu wa chotupa, ndipo zidutswa za cDNA akuti nthawi zambiri zimakhala zosakwana 167 bp.18 Kafukufuku wa Underhill adawonetsa kuti zidutswa za cfDNA nthawi zambiri zimakhala zazifupi kuposa cfDNA yanthawi zonse.19 Poyerekeza ndi anthu athanzi, utali wonse wa zidutswa za cfDNA m'magazi a odwala khansa ndi zazifupi, kotero cfDNA ingagwiritsidwe ntchito ngati chizindikiro cha kuyezetsa kotupa koyambirira.Kulemeretsa zigawo zina za cfDNA fragment kutalika kumatha kupititsa patsogolo kuzindikira kwa cDNA yolumikizidwa ndi zotupa zolimba zomwe sizikhala ndi metastatic.Kafukufuku wasonyeza kuti ctDNA imapezeka mu 75% ya khansa yapancreatic yapamwamba, colon, chikhodzodzo, m'mimba, chiwindi, ovarian, m'mawere, melanoma, mutu ndi khosi.20,21 Komabe, kuchuluka kwa ctDNA m'magazi kumadalira komwe pali chotupacho.22 Mu kafukufuku wa Bettegoud, odwala omwe ali ndi khansa ya colorectal, mawere, chiwindi, mapapo, ndi prostate adapezeka kuti ali ndi cDNA yambiri m'magazi awo kuposa khansa ina.Mosiyana ndi zimenezi, odwala khansa ya m'kamwa, khansa ya m'mimba, khansa ya m'mimba, ndi glioma, ndende ya cDNA m'magazi inali yochepa.makumi awiri ndi mphambu imodzi
Chifukwa ctDNA imakhala ndi masinthidwe amtundu womwewo monga ma cell chotupa chachikulu, cDNA imatha kugwiritsidwa ntchito kuzindikira masinthidwe amtundu wa chotupa komanso kusintha kwa epigenetic, kuphatikiza methylation, hydroxymethylation, kusiyanasiyana kwa nucleotide imodzi, komanso kusiyanasiyana kwa manambala.makumi awiri ndi mphambu zitatu
DNA methylation ndi chimodzi mwazofala kwambiri kusintha kwa epigenetic kumabweretsa kuponderezana kwa majini.Poyerekeza ndi maselo abwinobwino, pali kusiyana kwa kuchuluka kwa methylation ya chotupa cell genome, makamaka mu methylation ya chotupa suppressor majini, omwe amatha kuzindikirika atangoyamba kumene, kutanthauza kuti kusintha kwa DNA methylation kungakhale chizindikiro choyambirira. kuzindikira kwa tumorigenesis.Majini opondereza a chotupa okhudzana ndi HCC amatha kutsekedwa ndi olimbikitsa methylation, potero kulimbikitsa tumorigenesis.24 DNA methylation ndi chizindikiro chabwino chodziwikiratu zotupa chifukwa cha mawonekedwe ake, kuzindikirika, komanso kudziyimira pawokha zaka.Kuonjezera apo, DNA methylation ndiyofala kwambiri poyerekeza ndi kusintha kwa somatic chifukwa pali madera ambiri omwe amawunikira komanso malo angapo osinthidwa a CpG m'chigawo chilichonse cha genome.25 Kuwonjezera pa malo angapo a CpG, chiwerengero chachikulu cha malo odziimira okhaokha a hypermethylated mu ctDNA adziwika mu DBX2, THY1, MT1M, INK4A, VIM, FBLN1, ndi RGS10.26 Xu et al.Kuyerekeza kwa zitsanzo za cfDNA kuchokera kwa odwala 1098 HCC ndi zowongolera zathanzi 835 zinali majini okhudzana ndi HCC adapezeka kuti amagwirizana kwambiri ndi siginecha yofananira ya plasma cDNA methylation.25 Kutengera kusanthula kwa labotale, mtundu wolosera udapangidwa wokhala ndi zolembera 10 za methylation zokhala ndi chidwi komanso kutsimikizika kwa 85.7% ndi 94.3%, motsatana, ndipo zolemberazi zinali zogwirizana kwambiri ndi chotupa, siteji ya chotupa, komanso kuyankha kwamankhwala.Zotsatirazi zikuwonetsa kuti kugwiritsa ntchito zolembera za cDNA methylation kumakhala ndi chiyembekezo chachikulu pakuzindikira, kuyang'anira, ndi kuneneratu za HCC.Muchitsanzo cha methylation chomwe chili ndi majini atatu a aberrantly methylated (APC, COX2, RASSF1A) ndi miRNA imodzi (miR203) yoperekedwa ndi Lu et al27, kukhudzika ndi kutsimikizika kwa chitsanzo cha 27 pozindikira HBV-HCC yokhudzana ndi HBV zinali zofanana.80%.Kuonjezera apo, chitsanzochi chikhoza kuzindikira 75% ya odwala HCC osadziwika omwe ali ndi mlingo wa AFP wa 20 ng / mL.Jini la Ras-associated domain family 1A protein (RASSF1A) ndiye njira yayikulu yobwerezabwereza ya DNA mumtundu wa munthu.Araujo et al.adatsimikiza kuti hypermethylation ya wolimbikitsa RASSF1A ikhoza kukhala biomarker yofunikira pakuwunika koyambirira kwa HCC komanso cholinga cha mamolekyulu cha epigenetic therapy.28 Mu kafukufuku wina, seramu ya RASSF1A yolimbikitsa hypermethylation inapezeka mu 73.3% ya odwala omwe ali ndi HCC.29 Nucleotide element 1 (LINE-1) ndi mkhalapakati wina wogwira ntchito kwambiri wa retrotransposition.Hypomethylation ya LINE-1 inapezeka mu DNA ya 66.7% ya zitsanzo za HCC seramu ndipo zimagwirizanitsidwa ndi kubwereranso koyambirira komanso kupulumuka kosauka pambuyo pa kuchotsedwa kwakukulu.29 Hypermethylation ndi njira yodziwika bwino yomwe imagwira ntchito yapadera pakukula kwa chiwindi cha chiwindi ndi HCC.30 Mosiyana ndi zimenezi, hydroxymethylation ndi njira ya demethylation yomwe imapangitsa kuti majini ayambe kukonzanso ndi kufotokozera, ndipo kuzindikira kwa 5-hydroxymethylcytosine (5-hmC) mankhwala mu njirayi angagwiritsidwe ntchito kuzindikira chotupa.Methylation ndi hydroxymethylation ya cDNA imalumikizidwa ndi tumorigenesis ndipo imatha kuthandizira kuwunika koyambirira kwa HCC.Pakafukufuku wa anthu 2554, ma 31 genome-wide 5-hmCs adapezeka mu zitsanzo za cfDNA, ndipo majini 32 adadziwika poyerekeza ma 5-hmC otsatizana mwa odwala HCC ndi magulu omwe ali pachiwopsezo chachikulu monga omwe ali ndi matenda osatha.Zitsanzo za matenda a chiwindi.ndi cirrhosis.Chitsanzochi chinali chapamwamba kuposa AFP posiyanitsa HCC ndi minofu yopanda chotupa.
Kusintha kwa zigawo zokhotakhota kumatha kubweretsa zolakwika zolembedwa, zomwe zimatha kubweretsa kusintha kwamapuloteni ndipo pamapeto pake khansa.Mitundu imodzi ya ma nucleotide ndiyofunikira kwambiri pakuwunika koyambirira kwa chotupa chifukwa cha kudalirika kwa minofu yawo komanso kuchuluka kwa chotupa ndi minofu.Kafukufuku wambiri wokhudzana ndi HCC pogwiritsa ntchito mibadwo yotsatira (NGS) yotsatizana ndi ma genome onse a khansa apeza ma gene osinthika amtundu wa cell monga TP53 ndi CTNNB1, komanso angapo kuphatikiza ARID1A, MLL, IRF2.Majini atsopano, ATM, CDKN2A, FGF19, PIK3CA, RPS6KA3 ndi JAK1 amawonetsa masinthidwe apakati. Kusanthula kwa jini kosinthika kumasonyeza kuti kusintha kwa chromatin kukonzanso, Wnt/β-catenin ndi JAK/STAT transduction, P53-cell cycle pathway, epigenetic modifiers, oxidative stress pathways, PI3K/AKT/MTOR njira ndi RAS/RAF/ MAPK kinase pathway imagwira ntchito yofunika kwambiri mu HCC oncogenesis.32,33 Pakufufuza komwe kusintha kwa chotupa kunapezeka, Huang et al adapeza kuti kuchuluka kwa zotupa zokhudzana ndi chotupa kumadalira ctDNA kunali 19.5%, ndipo kutsimikizika kwake kunali 90%. .34 Kuonjezera apo, odwala omwe adagwidwa ndi mitsempha ya mitsempha amatha kukhala ndi kusintha kwa ctDNA (P = 0.041) ndi kupulumuka kwaufupi kosabwerezabwereza (P <0.001). Kusanthula kwa jini kosinthika kumasonyeza kuti kusintha kwa chromatin kukonzanso, Wnt/β-catenin ndi JAK/STAT transduction, P53-cell cycle pathway, epigenetic modifiers, oxidative stress pathways, PI3K/AKT/MTOR njira ndi RAS/RAF/ MAPK kinase pathway imagwira ntchito yofunika kwambiri mu HCC oncogenesis.32,33 Pakufufuza komwe kusintha kwa chotupa kunapezeka, Huang et al adapeza kuti kuchuluka kwa zotupa zokhudzana ndi chotupa kumadalira ctDNA kunali 19.5%, ndipo kutsimikizika kwake kunali 90%. .34 Kuonjezera apo, odwala omwe adagwidwa ndi mitsempha ya mitsempha amatha kukhala ndi kusintha kwa ctDNA (P = 0.041) ndi kupulumuka kwaufupi kosabwerezabwereza (P <0.001).Kusanthula kwa jini kosinthika kukuwonetsa kuti kusintha kwa kukonzanso kwa chromatin, Wnt/β-catenin ndi JAK/STAT siginecha, P53 cell cycle pathway, epigenetic modifiers, oxidative stress pathways, PI3K/AKT/MTOR pathway, ndi RAS/RAF/MAPK kinase pathway. gawo lofunika kwambiri mu HCC tumorigenesis.32,33 Mu kafukufuku yemwe anapeza kusintha kwa chotupa chokhudzana ndi chotupa, Huang et al.anapeza kuti mafupipafupi a kusintha kwa chotupa chodalira ctDNA anali 19.5% ndipo kutsimikizika kwake kunali 90%..34 Кроме того, у пациентов сосудистой инвазией чаще мстречались мутации цДНК (P=0,041) ndi более короткая безрецивыдижи 0 (1). .34 Kuonjezera apo, odwala omwe ali ndi mitsempha ya mitsempha anali ndi kusintha kwa cDNA (P = 0.041) ndi kupulumuka kwafupipafupi popanda matenda (P <0.001).Kusanthula kogwira ntchito kwa majini osinthika kunavumbulutsa kukonzanso kwa chromatin, Wnt/β-catenin ndi JAK/STAT siginecha, P53 cell cycle pathway, epigenetic modifiers, oxidative stress pathway, PI3K/AKT/MTOR njira, ndi RAS/RAF/MAPK kinase pathway imagwira ntchito yofunika kwambiri pa oncogenesis ya HCC. 32,33 在 一 项 检测 检测 到 肿瘤 突变 突变 突变 突变 突变 中 中 人 依赖于 依赖于 依赖于 依赖于 为此外突变（P=0.041）和更短的无复发生存期（P<0.001). 32.33 在 一 一 检测 检测 到 到 突变 突变 的 研究 发现 依赖于 依赖于 为 发生 为 为 为 发生 发生 发生短的无复发生存期（P<0.001）.32,33 Mu kafukufuku yemwe adapeza masinthidwe okhudzana ndi chotupa, Huang et al.adapeza kuti kusintha kwa chotupa kunali 19.5% kumadalira cDNA ndi 90% 34. Kuwonjezera apo, odwala omwe adagwidwa ndi mitsempha ya mitsempha amatha kukhala ndi cDNA.мутация (P = 0,041) ndi более короткая безрецидивная выживаемость (P <0,001). kusintha (P=0.041) ndi kupulumuka kwaufupi popanda matenda (P<0.001).Jini ina yodziwika bwino yoyendetsa HCC ndi TP53, yomwe ili ndi masinthidwe opitilira 30%.Kafukufuku wawonetsa kuti ma frequency a TP53 masinthidwe mu ctDNA m'magazi ndi mkodzo amachokera ku 5% mpaka 60%.35 Kafukufuku wa Johan adawonetsa kuti ctDNA mutation sipekitiramu kumapeto kwa HCC ili ndi masinthidwe ofanana ndi a HCC oyambirira, kuphatikiza wolimbikitsa TERT (51%), TP53 (32%), CTNNB1 (17%), PTEN (8%), masinthidwe mu Chithunzi cha AXIN1., ARID2, KMT2D ndi TSC2 (6% iliyonse).36 The β-catenin (CTNNB1) oncogene imagwira ntchito yofunikira panjira yowonetsera Wnt.The transcription coactivator CTNNB1 imatha kulimbikitsa mafotokozedwe a majini, omwe angayambitse kuchuluka kwa maselo, kuletsa apoptosis, ndi angiogenesis.CTNNB1 imathanso kuyanjana ndi TERT kuti ipangitse kusintha kwa hepatocyte.33 Wotsatsa wa TERT nthawi zambiri amasinthidwa m'matumbo olimba.Kusintha kwa TERT, chimodzi mwa kusintha koyambirira kwa majini pakusintha koyipa kwa HCC, kungayambitse kuyambiranso kwa telomerase mu cirrhotic hepatocytes ndipo kungalimbikitse kuchulukana ndikuletsa kukalamba.Kusintha kwa 33-37 TERT wolimbikitsa kwanenedwa kuti kumachitika mu 59-90% ya odwala omwe ali ndi zilonda zam'mimba zowonjezera komanso HCC oyambirira ndipo amagwirizanitsidwa ndi kupulumuka.38
Kusintha kwa nambala (CNA) ndi gawo lofunikira la masinthidwe a somatic.Kafukufuku wasonyeza kuti kufalikira komanso kukhazikika kwa CNA ndi siginecha ya genomic yomwe imatha kulosera kulowetsedwa kwa chitetezo chamthupi ndi kuchotsedwa mumitundu ina ya khansa.39 Kulowetsa mogwira ntchito, ntchito yapamwamba ya cytolytic, kutupa kwakukulu ndi zizindikiro za majini zomwe zimagwirizanitsidwa ndi antigen ulaliki mu HCC.Kuwunika kwa ma data a single nucleotide polymorphisms mu maphunziro a 477 kunawonetsa kulemedwa kochepa pa CNS.Mosiyana ndi izi, zotupa zosakhazikika za chromosomal zomwe zimakhala ndi katundu wambiri wa CNA zimasonyeza zizindikiro za kukana chitetezo cha mthupi ndipo zimagwirizanitsidwa ndi kuchulukana, kukonza DNA, ndi TP53 kukanika.Xu et al.adawonetsa kuti gulu la HCC linali ndi ma CNA apamwamba kuposa gulu la matenda a chiwindi.40 Pogwiritsa ntchito kutsatizana kwamtundu wonse wa selo limodzi, ma CNA adapezeka kuti amawoneka koyambirira kwa hepatocarcinogenesis ndipo amakhalabe okhazikika pakapita chotupa.41 Chung et al.anapeza kuti milingo ya cfDNA inali yokwezeka kwambiri mwa odwala HCC komanso kuti ma CNA amitundu yonse mu cfDNA anali odziyimira pawokha odziyimira pawokha mwa odwala a HCC omwe amathandizidwa ndi sorafenib.Odwala a 42 omwe ali ndi katundu wambiri wa CNA anali ndi mwayi wochuluka wa matenda ndi imfa kusiyana ndi omwe ali ndi katundu wochepa wa CNA.Ollerich ndi al.anapeza kuti copy number instability index (CNI) angagwiritsidwe ntchito kuwunika CNA mu cfDNA odwala khansa.Iwo adanena kuti odwala omwe ali ndi khansa yapamwamba anali ndi ma CNI apamwamba kwambiri kuposa gulu lolamulira, lomwe limayesa kuyankha kwa odwala ku systemic chemotherapy ndi immunotherapy.43 Zotsatira izi zikusonyeza kuti CNAs zopezeka mu madzi biopsy toyesa akhoza kukhala tsogolo zizindikiro kwa odwala khansa kwambiri.HCC pa maziko a zokhudza zonse mankhwala.
Pakalipano, njira zomwe zimagwiritsidwa ntchito pozindikira ctDNA zitha kugawidwa m'njira zomwe zimayang'aniridwa komanso zomwe sizikutsata.Mwachidule, njira zomwe zimayang'aniridwa monga digito polymerase chain reaction (dPCR), BEAMing digital PCR, Amplification Refractory Mutation System-PCR, Capp-Seq ndi Tam-Seq zimakhudzidwa kwambiri ndi majini omwe afotokozedwatu.Njira zomwe sizingalephereke monga kutsatizana kwa ma genome ndi NGS zimapereka chithunzithunzi chonse cha mawonekedwe onse a genomic.44 Poyerekeza ndi mapanelo omwe mukufuna, kutsatizana konse kwa ma genome sikungazindikire kusintha kwa mfundo ndi zoyikapo, komanso kukonzanso ndikusintha manambala.prognosis, ndi CTC ndi cfDNA ndi zizindikiro zabwino zomwe zingagwiritsidwe ntchito kuwunika kwamphamvu kwa HCC.45 Kuphatikiza apo, kusanthula kwa cfDNA kungakhale kothandiza pakuzindikira HCC.Yan et al.adawonetsa kuti cfDNA mu plasma ya odwala omwe ali ndi HCC inali yokwera kwambiri kuposa odwala omwe ali ndi chiwindi fibrosis komanso amawongolera athanzi.Poyerekeza ndi AFP, ctDNA ikuyembekezeka kukhala cholembera bwino cha HCC yoyambirira.46 Mu kafukufuku woyembekezeredwa wa ma biopsies amadzi 47 omwe adayesa cfDNA ndi mapuloteni pagulu la anthu, adawonetsedwa kuti ndi othandiza kusiyanitsa odwala omwe ali ndi HCC ndi odwala opanda HCC.Potsatira odwala 331 a ultrasound abwinobwino komanso opanda AFP, kukhudzika ndi kutsimikizika kwa cfDNA pozindikira HCC kunali 100% ndi 94%, motero, cDNA imatha kuzindikira HCC mwa anthu omwe ali ndi vuto la HBsAg.Mu kafukufuku wa Yeo48, pafupipafupi (92.5%) ya hypermethylation ya RASSF1A yolimbikitsa idapezeka mwa odwala omwe ali ndi HCC.Kuphatikiza apo, Xu et al.adapanga njira yodziwira matenda kuti alosere HCC pogwiritsa ntchito gulu la zolembera za methylation zomwe zimakhala ndi 90.5% ndi 83.3% motsatana.Gululi limalola odwala omwe ali ndi HCC kuti asiyanitsidwe ndi odwala omwe ali ndi matenda ena a chiwindi, omwe ndi abwino kuposa AFP.Adapezanso kuti zowongolera zomwe zapezeka kuti zili ndi kachilomboka zimatha kukhala ndi ziwopsezo za HCC, monga matenda a HBV kapena mbiri yakale yomwa mowa.25 Timalingalira kuti zinthu zomwe zimakhala pachiwopsezo chachikulu cha HCC zitha kulimbikitsa hypermethylation ya cfDNA, zomwe zimathandizira kuti HCC ipitirire, motero cfDNA itha kukhala ndi gawo lalikulu pakuwunika magulu omwe ali pachiwopsezo chachikulu.Cai et al.fotokozani mwachidule zamitundu yonse ya masinthidwe a ctDNA ndikupereka njira yolimba yowunika kuchuluka kwa chotupa mwa odwala.49 Njirayi imatha kuzindikira tumorigenesis yapakati pa miyezi ya 4.6 isanayambe kusintha kwazithunzi ndipo yawonetsa ntchito yapamwamba yowunikira poyerekeza ndi serum biomarkers AFP, AFP-L3, ndi PIVKA-II.Phindu lachidziwitso la kuyesa kwa cDNA lasonyezedwa pamene kuwunika kwazithunzi kulibe, kotero kuyesa kwa cDNA kuli kofunikira pakuzindikiritsa kwa HCC yoyambirira m'magulu omwe ali pachiwopsezo chachikulu.Posachedwapa, asayansi adagwiritsa ntchito ukadaulo wa NGS kusanthula zisonyezo zamitundu yosiyanasiyana yamitundu yosiyanasiyana (kuphatikiza 5-hydroxymethylcytosine, 5'-motif, fragmentation, nucleosome trace, HIFI) mu zitsanzo zachipatala za 3204 ndi cfDNA.Mitundu ya 50 yovomerezekanso ya HIFI yokhala ndi masitima atatu odziyimira pawokha, mayeso, ndi ma seti oyesa adawonetsa tsankho lokhazikika komanso lodalirika pakati pa HCC ndi anthu omwe si a HCC okhala ndi 95.79% ndi 95.42% kukhudzidwa mu mayeso enieni a HCC ndi seti zoyeserera, motsatana.Kugonana kunali 95.00% ndi 97.83%, motero.Phindu lachidziwitso la njira ya HIFI ndilapamwamba kuposa la AFP posiyanitsa HCC ndi cirrhosis.Kuphatikiza apo, ctDNA imagwiritsidwanso ntchito pochiza opaleshoni.Atsushi et al.adatsimikiza za preoperative serum milingo ya ctDNA mwa odwala omwe ali ndi HCC ndipo adapeza kuti kuchuluka kwa kubwereza komanso kuchuluka kwa metastasis ya extrahepatic mu gulu labwino la cDNA kunali kokulirapo kuposa gulu loyipa la cDNA, ndipo milingo ya cDNA inali yogwirizana kwambiri.ndi kukula kwa chotupa.51 Pokhala chodziwikiratu kwambiri, ctDNA imatha kulosera za kuthekera kwa HCC kuwononga zombo.Wang ndi al.adachita kutsata ma genome a odwala 46 omwe ali ndi HCC, ndipo kusanthula kwamitundumitundu kunawonetsa kuti kuchuluka kwa mafupipafupi amtundu wa cDNA pakuwukiridwa ndi ma microvessels ndi 0.83%, kukhudzika 89.7% ndi kutsimikizika 80.0%.chiopsezo chodziyimira pawokha pakuwukira kwa microvascular mu HCC yokhazikika, kutanthauza kuti cDNA ikhoza kuthandizira kuwongolera chithandizo choyenera.Pomaliza, ctDNA imakhudzidwa kwambiri ndi zomwe zimachitika komanso kakulidwe ka HCC ndipo itha kugwiritsidwa ntchito powunika msanga, kuyesa maopaleshoni, ndikuwunika matenda.
Ma CTC ndi maselo oyipa omwe amachokera ku zotupa zoyambirira kapena ma metastases omwe amafalikira m'magazi.Ma cell a chotupa amatulutsa matrix metalloproteinases (MMPs), omwe amaphwanya nembanemba yapansi, zomwe zimapangitsa kuti maselo a chotupa alowe mwachindunji m'magazi ndi mitsempha yamagazi.Komabe, ma CTC ambiri amachotsedwa mwachangu ndi anoikis, chitetezo chamthupi, kapena kumeta ubweya.53 The epithelial-mesenchymal transition (EMT) imalola ma CTCs kuti adzilekanitsidwe mosavuta ndi minofu yoyambira yotupa, kuukira ma capillaries, ndikukhala ndi moyo wabwino kwambiri, metastasis, invasiveness, ndi kukana mankhwala.Kafukufuku wasonyeza kuti pali kusiyana kwakukulu pakati pa maselo osiyanasiyana a chotupa mu zotupa zoyambirira za metastatic.Chifukwa chake, kusanthula kwa CTC kumatha kupangitsa kumvetsetsa bwino za chotupa cell heterogeneity.54
Zolemba zenizeni za ma CTC ogwirizana ndi HCC ndi glypican-3 (GPC3), asialoglycoprotein receptor (ASGPR), epithelial cell adhesion molecule (EpCAM) ndi zolembera za stem cell monga CD44, CD90, 55 ndi intercellular adhesion molecule 1 (ICAM1).) .56 Chizindikiro cha GPC3 ndi puloteni yokhala ndi nembanemba ya cell yomwe imagwiritsidwa ntchito pofufuza matenda ndi kuzindikira za HCC.57 Kufotokozera kwa GPC3 kumakhala kofala kwambiri m'maselo a chotupa a HCC omwe ali ndi kusiyana kwapakatikati ndi kochepa ndipo amalimbikitsa kusamuka kwa extrahepatic;kuonjezera apo, kukhalapo kwa GPC3+ CTCs kumasonyeza HCC ya metastatic.58 ASGPR ndi mapuloteni a transmembrane omwe amawonetsedwa pamwamba pa hepatocytes ndipo amawonetsedwa kwambiri mu HCC yosiyana kwambiri.EpCAM ndi amodzi mwa mapuloteni omwe amagwiritsidwa ntchito kwambiri ndi membrane kuti agwire ma CTC.EpCAM yadziwika kuti ndi chizindikiro chapamwamba cha maselo a HCC omwe ali ndi tsinde la maselo, 59 omwe amagwirizana ndi zinthu zosiyanasiyana zachipatala za HCC, monga kuukira kwa mitsempha, kuyesa kwa AFP, ndi siteji yapamwamba ya khansa ya chiwindi ku chipatala cha Barcelona (BCLC).The 60 CTC EMT phenotype ndi metastatic kwambiri.54 EMT njira mu CTC zimalimbikitsa HCC metastasis.Kufotokozera kwa zizindikiro za EMT monga vimentin, twist, E-box zinc finger binding (ZEB) 1, ZEB2, nkhono, slug, ndi E-cadherin zaphunziridwa mu ma CTC opangidwa ndi chiwindi kuchokera kwa odwala HCC.58 Dongosolo la CanPatrol™ lopangidwa ndi Cheng [61] adayika ma CTC m'magulu atatu a phenotypic kutengera zolembera zomwe zimawonetsedwa kwambiri: epithelial phenotype (EpCAM, CK8/18/19), mesenchymal phenotype (vimentin, coiled), ndi phenotypes wosakanikirana.Mu odwala 176, CTC yonse inali yopambana AFP posiyanitsa HCC ndi matenda a chiwindi.Miyezo ya AUC pa CTC yonse, AFP, ndi CTC yonse ndi AFP zophatikizidwa zinali 0.774 (95% CI, 0.704-0.834), 0.669 (95% CI, 0.587-0.750), ndi 0.821 (95% CI, 0.886-0.786 ).), motero.Gulu la CTC lochokera pa EMT limatha kulosera za matenda a HCC, kuyambiranso koyambirira, kufalikira, komanso kufupikitsa nthawi yonse.
Pakalipano, njira zodziwira ma CSC zimaphatikizapo njira zakuthupi ndi njira zamoyo.Njira zakuthupi, zomwe nthawi zambiri zimatchedwa kulemeretsa kutengera zinthu zamoyo, makamaka zimadalira mawonekedwe a CSC, monga kukula, kachulukidwe, mtengo, kuyenda ndi kupunduka.Kutengera ndi zinthu zakuthupi, pali njira zingapo monga kusefera-based systems, dielectrophoresis, etc. Yotsirizirayi, yomwe imatchedwanso kuti immunoaffinity-based enrichment, imachokera ku ma antigen-antibody kumanga popeza njirayo imagwiritsa ntchito ma antibodies motsutsana ndi zotupa zenizeni. monga EpCAM, ASGPR, human epidermal growth factor receptor 2 (HER2), prostate specific antigen (PSA), human pancytokeratin (P-CK) ndi carbamoyl phosphate synthase 1 (CPS1).62 Mtundu wina, wotchedwa no-enrichment method, umagwiritsa ntchito flow cytometry kusiyanitsa ma CTC ndi leukocyte potengera kuchuluka kwa nyukiliya-to-cytoplasmic ndi kukula kwake.Pakadali pano, mayeso okhawo ovomerezeka ndi FDA ozindikira ma CTC ndi makina a Cell-Search™, omwe amagwiritsa ntchito cholembera ma cell a EpCAM. Komabe, kuzindikirika kwa CTC kogwirizana ndi zizindikiro kungapangitse kuchuluka kwa positivity.54 Kusakaniza kwa ma antibodies motsutsana ndi ASGPR ndi CPS1 kunapeza chiwerengero cha CTC cha 91% mwa odwala HCC.63 Zhang et al adagwiritsa ntchito CTC-Chip yokhala ndi ma antibodies motsutsana ndi ASGPR, P -CK ndi CPS1, ndikusiyanitsa odwala a HCC kuchokera kwa omwe ali ndi matenda a chiwindi kapena khansa yosakhala ya HCC pa mlingo wa 100%.64 Kafukufuku wa Wang adapeza EpCAM + CTCs mu 60% ya odwala 42 HCC ndipo adapeza mgwirizano waukulu pakati pa positivity mlingo ndi chiwerengero cha ma CTC omwe ali ndi TNM stage.65 Guo et al anapeza kuti chiwerengero cha PCR chochokera ku CTC chinakwezedwa mwa odwala 125/171 (73%) omwe mlingo wa AFP unali <20 ng/mL ndi kumva kwa 72.5% ndi a zenizeni za 95.0%, poyerekeza ndi 57.0% ndi 90.0% ya AFP pa cutoff 20 ng / mL.66 Kuphatikiza kwa AFP ndi CTCs kungapangitse kuzindikira kwa HCC.45 Amakhulupirira kuti CTCs ali ndi mwayi kuposa AFP pakuwunika koyambirira kwa magulu pachiwopsezo chachikulu cha HCC. Komabe, kuzindikirika kwa CTC kogwirizana ndi zizindikiro kungapangitse kuchuluka kwa positivity.54 Kusakaniza kwa ma antibodies motsutsana ndi ASGPR ndi CPS1 kunapeza chiwerengero cha CTC cha 91% mwa odwala HCC.63 Zhang et al adagwiritsa ntchito CTC-Chip yokhala ndi ma antibodies motsutsana ndi ASGPR, P -CK ndi CPS1, ndikusiyanitsa odwala a HCC kuchokera kwa omwe ali ndi matenda a chiwindi kapena khansa yosakhala ya HCC pa mlingo wa 100%.64 Kafukufuku wa Wang adapeza EpCAM + CTCs mu 60% ya odwala 42 HCC ndipo adapeza mgwirizano waukulu pakati pa positivity mlingo ndi chiwerengero cha ma CTC omwe ali ndi TNM stage.65 Guo et al anapeza kuti chiwerengero cha PCR chochokera ku CTC chinakwezedwa mwa odwala 125/171 (73%) omwe mlingo wa AFP unali <20 ng/mL ndi kumva kwa 72.5% ndi a zenizeni za 95.0%, poyerekeza ndi 57.0% ndi 90.0% ya AFP pa cutoff 20 ng / mL.66 Kuphatikiza kwa AFP ndi CTCs kungapangitse kuzindikira kwa HCC.45 Amakhulupirira kuti CTCs ali ndi mwayi kuposa AFP pakuwunika koyambirira kwa magulu pachiwopsezo chachikulu cha HCC.Komabe, kuzindikiritsa kophatikizana kwa zizindikiro za CTC kungapangitse kuchuluka kwa zotsatira zabwino.54 Kusakaniza kwa anti-ASGPR ndi CPS1 antibodies kunapeza chiwerengero cha CTC cha 91% mwa odwala HCC.63 Zhang et al.adagwiritsa ntchito CTC-Chip yokhala ndi ma antibodies motsutsana ndi ASGPR, P-CK ndi CPS1, komanso adasiyanitsa odwala omwe ali ndi HCC kuchokera kwa omwe ali ndi matenda a chiwindi kapena omwe alibe HCC pamlingo wa 100%.частота и количество ЦОК со стадией TNM.65 Guo и соавторы обнаружили, что показатель ПЦР, полученный из ЦОК, был повышен у 125/171 (73%) пациентов, у которых уровень АФП был <20 нг/мл с чувствительностью 72,5% и специфичность 95,0% по сравнению с 57,0% и 90,0% для АФП при пороговом уровне 20 нг/мл.66 Комбинация АФП и ЦОК может улучшить обнаружение ГЦК.45 Считается, что ЦОК имеют преимущество перед АФП при раннем скрининге групп. pafupipafupi ndi chiwerengero cha ma CTC omwe ali ndi TNM stage.65 Guo et al adapeza kuti PCR yochokera ku CTCs idakwezedwa mu 125/171 (73%) odwala omwe anali ndi AFP milingo <20 ng / mL ndi kukhudzika kwa 72.5% ndi kutsimikizika kwa 95.0% poyerekeza ndi 57.0% ndi 90.0% ya AFP pa mlingo wodulidwa wa 20 ng / mL.66 Kuphatikiza kwa AFP ndi CTCs kungapangitse kuzindikira kwa HCC.45 CTCs amaonedwa kuti ali ndi mwayi kuposa AFP pakuwunika koyambirira. magulu.ndi chiopsezo chachikulu cha HCC.Komabe, kuzindikira kogwirizana ndi zolembera zophatikiza ma CTC kungapangitse kuchuluka kwa zotsatira zabwino.54 Chisakanizo cha anti-ASGPR ndi CPS1 antibodies chinapeza 91% CTC yodziwika bwino mwa odwala omwe ali ndi HCC.63 Zhang et al.adagwiritsa ntchito tchipisi ta CTC okhala ndi ma antibodies motsutsana ndi ASGPR, P-CK ndi CPS1 komanso odwala odziwika omwe ali ndi HCC ku matenda a chiwindi owopsa komanso omwe si a HCC okhala ndi 100%.Kafukufuku wa 64 Wang adapeza 60% ya EpCAM+ CTCs mwa odwala 42 HCC ndipo adapeza kulumikizana kwakukulu pakati pa zochitika ndi kuchuluka kwa ma CTC pagawo la TNM. 65 Guo 等人发现，在AFP 水平<20 ng/mL 的125/171 (73%) 名患者中，CTC 衍生的PCR 评分升高，敏感性，敏感性，敏感性，敏感性，敏感 5%.值为20 ng/mL 时的特异性為57.0% 和90.0%. 65 GUO 等 人 发现 在 在 在 水平 水平 水平 水平 水平 y 的 的 的 为 为 为截止 截止 截止 截止 截止 截止 截止 截止 截止 截止 截止 截止 截止 截止 截止 截止 截止 截止 截止 截止为65 Guo et al.обнаружили, что у 125/171 (73%) пациентов с уровнем АФП <20 нг/мл показатели ПЦР, полученные с помощью ЦОК, были повышены с чувствительностью 72,5% и специфичностью 95,0%, в то время как АФП на уровне отсечки Специфичность составляла 20 нг/мл. adapeza kuti mu 125/171 (73%) odwala omwe ali ndi milingo ya AFP <20 ng/mL, ma PCR opangidwa ndi CTC adakwezedwa ndi chidwi cha 72.5% komanso kutsimikizika kwa 95.0%, pomwe AFP idadulidwa. anali 20 ng/mL.ml anali 57.0% ndi 90.0%.66 Kuphatikiza kwa ORP ndi CTC kumathandizira kuzindikira kwa HCC.45 CTCs amaganiziridwa kuti ndi apamwamba kuposa AFP pakuwunika koyambirira kwa anthu omwe ali pachiwopsezo chachikulu cha HCC.Choncho, kwa magulu a HCC omwe ali ndi CTC omwe ali ndi chiopsezo chachikulu, kuyesa kwa CTC kuyenera kuphatikizidwa nthawi zonse ndi ultrasound ndi AFP kuzindikira.Komabe, ma CTC amaonedwa kuti ndi ofunika kulosera za metastasis ya chotupa ndi kubwereranso, ndipo kuzindikira kwa CTC sikuvomerezeka mwapadera ngati chida chodziwira.62 Chifukwa chake, CTC ikhoza kukhala yolosera bwino kuposa zolembera zina zomwe zimagwiritsidwa ntchito pano. Zhou et al adapeza kuti odwala omwe ali ndi chiwerengero chokwera cha EpCAM + CTCs ndi maselo olamulira a T amasonyeza kuti ali ndi chiopsezo chachikulu chokhala ndi HCC kubwereranso, kusiyana ndi omwe ali ndi chiwerengero chochepa cha CTCs, ndi chiwerengero cha 66.7% vs 10.3% (P <0.001) .67) Kafukufuku wofananawo adanenedwa ndi Zhong et al.68 Kuonjezera apo, Qi adapeza kuti 101 mwa odwala 112 (90.81%) omwe ali ndi HCC, kuphatikizapo omwe ali ndi matenda oyambirira, anali abwino kwa CTCs komanso kuti tinthu tating'onoting'ono ta HCC tinapezeka pambuyo pa 3. mpaka miyezi 5 yotsatila. Zhou et al adapeza kuti odwala omwe ali ndi chiwerengero chokwera cha EpCAM + CTCs ndi maselo olamulira a T amasonyeza kuti ali ndi chiopsezo chachikulu chokhala ndi HCC kubwereranso kusiyana ndi omwe ali ndi chiwerengero chochepa cha CTCs, ndi chiwerengero cha 66.7% vs 10.3% (P <0.001) .67 A. Kafukufuku wofananawo adanenedwa ndi Zhong et al.68 Kuonjezera apo, Qi adapeza kuti 101 mwa odwala 112 (90.81%) omwe ali ndi HCC, kuphatikizapo omwe ali ndi matenda oyambirira, anali abwino kwa CTCs komanso kuti tinthu tating'onoting'ono ta HCC tinapezeka pambuyo pa 3 Miyezi 5 yotsatila. Чжоу ndi др.обнаружили, что у пациентов с повышенным количеством ЦОК EpCAM+ и регуляторных Т-клеток риск развития рецидива ГЦК был выше, чем у пациентов с низким количеством ЦОК, с коэффициентом рецидивов 66,7% против 10,3% (P <0,001)67. Zhou et al adapeza kuti odwala omwe ali ndi EpCAM + CTCs okwera ndi maselo a T olamulira anali ndi chiopsezo chachikulu cha HCC kubwereranso kusiyana ndi omwe ali ndi CTCs otsika, ndi chiwerengero cha 66.7% vs 10.3% (P <0.001) 67.Kafukufuku wofananawo adachitidwa ndi Zhong et al.68. Kuonjezera apo, Qi adapeza kuti 101 mwa odwala 112 (90.81%) omwe ali ndi HCC, kuphatikizapo omwe ali ndi matenda oyambirira, anali ndi CTCs, ndipo ma nodule ang'onoang'ono a HCC adapezeka pambuyo pa 3 kwa miyezi 5 yotsatila. ZHOU 等 发现 发现, 与 CTC 数量 少 少 相比 相比 相比 分别 高 分别 分别 分别 分别调节性 ZHu 等 发现 与 与 与 与 ctc 数量 少 相比 相比 相比c 和 发生 发生 数量 数量 数量 数量 数量 为 为 为 为 为 10.3% ( pa <0.001).......... Чжоу ndi др.обнаружили, что пациенты с повышенным количеством ЦОК EpCAM+ и регуляторных Т-клеток имели более высокий риск рецидива ГЦК по сравнению с пациентами с меньшим количеством ЦОК, с частотой рецидивов 66,7% и 10,3% соответственно (P <0,001). Zhou et al.anapeza kuti odwala omwe ali ndi EpCAM + CTCs okwera ndi maselo olamulira a T anali ndi chiopsezo chachikulu cha HCC kubwereranso poyerekeza ndi odwala omwe ali ndi CTCs ochepa, omwe ali ndi chiwerengero cha 66.7% ndi 10.3%, motero (P <0.001).Kafukufuku wofananawo adanenedwa ndi Zhong et al.68 Kuonjezera apo, Qi adapeza kuti 101 mwa odwala 112 HCC (90.81%), kuphatikizapo odwala matenda oyambirira, anali ndi zotsatira zabwino za CTC ndipo adapeza timadontho tating'ono ta HCC pambuyo pa maulendo atatu.Kuwonera mpaka miyezi 5.Anapezanso ma CTC mwa odwala 12 omwe ali ndi matenda aakulu a HBV ndipo adapeza zotupa zazing'ono za HCC mkati mwa miyezi 5 mwa odwala 2 omwe ali ndi CTC.69 Chifukwa chake, ma CTC atha kugwiritsidwa ntchito kulosera HCC, 70 koma atha kugwiritsidwa ntchito mwachizolowezi ngati zolosera zam'tsogolo.
Monga cfDNA, cfRNA imatulutsidwa m'magazi kudzera m'machitidwe osiyanasiyana.Mamolekyu awa m'magazi ozungulira amayimira minofu ya khansa yomwe idachokera.Poyerekeza ndi zolembera zomwe zimazindikiridwa ndi njira zomwe sizimasokoneza, ma cfRNA amawongolera kwambiri, amakhala ndi minofu, komanso amakhala ochulukirapo m'malo opezeka kunja.Kufunika ndi kuzindikira kwa 71 miRNAs (miRNAs) mu HCC zafotokozedwa m'maphunziro ambiri.Ma miRNA ndi ma RNA (ncRNAs) osakhazikika omwe amayang'anira zochitika zosiyanasiyana zamamolekyulu poletsa kumasulira kwa ma RNA a messenger (mRNAs).ma miRNAs ali m'matupi a apoptotic omwe ali mu exosomes, koma amathanso kumangirira ku mapuloteni a seramu ndi lipids m'magazi ozungulira ndipo angagwiritsidwe ntchito poyesa HCC.Ma microRNA amakhudzidwa ndi kusinthika kwa chiwindi, lipid metabolism, apoptosis, kutupa, ndi chitukuko cha HCC.72 Oncogenic miRNAs monga miR-21, miR-155 ndi miR-221 amadziwika bwino ku HCC.Makamaka, miR-21 imagwira ntchito yofunika kwambiri pakupanga kolajeni mu extracellular matrix ndi fibrosis ndipo imalimbikitsa hepatocarcinogenesis poyambitsa ma cell a hematopoietic stem.72,73 Tumor suppressor miRNAs mu HCC imaphatikizapo miRNA-122, miRNA-29, banja la Let-7, ndi banja la miRNA-15.Banja la Let-7 lili ndi ma miRNA ambiri omwe amalimbana ndi banja la RAS.Banja la miR-15 limaphatikizapo miR-15a, miR-15b, miR-16, miR-195, ndi miR-497, omwe ali ndi matsatidwe owonjezera a ma mRNA ena.Kuphatikiza apo, ma RNA aatali osalemba zilembo (lncRNAs) ndi ma RNA ozungulira (cirRNAs) nawonso ndizofunikira pakuwunika koyambirira kwa HCC.lncRNAs amaimira gulu lalikulu kwambiri la ncRNAs, kuphatikizapo mRNA-monga ncRNAs, ndipo amakhudzidwa ndi matenda a matenda ambiri a anthu.LncRNAs imagwira ntchito yolamulira mu chiwindi cha microenvironment ndi matenda aakulu a chiwindi.74 CircRNAs nawonso ndi gulu la ma ncRNA okhala ndi ntchito zingapo pakuwongolera mawu amtundu.Posachedwa, ma circRNA amawonedwa ngati zida zowunikira HCC.
Kuzungulira kwa RNA yaulere kumakhala ndi kukhazikika kodabwitsa, kuphatikiza kukana kutentha, pH, ndi RNase, zomwe zimapangitsa kudzipatula kwa fnRNA kumagazi am'magazi kukhala osatopetsa pogwiritsa ntchito njira zoyeretsera za RNA.Njira zomwe zimagwiritsidwa ntchito kwambiri ndi NGS, microarray ndi RT-qPCR.NGS imalola ma microRNA kuti ayezedwe mu genome yonse.Komabe, njira imeneyi ndi okwera mtengo ndipo kusanthula si muyezo.Mosiyana ndi izi, RT-qPCR ndiyotsika mtengo, imakulitsa mwachangu ma nucleic acid, ndipo imapereka zabwino zambiri monga kukhudzika kwakukulu, kulondola kwambiri, kusinthasintha kokulirapo, komanso kumafuna zitsanzo zochepa.Ma Microarrays ndi njira ina yomwe imagwiritsidwa ntchito pozindikira miRNA potengera kusakanikirana kwachangu komanso kwachindunji kwa ma miRNA omwe ali ndi ma DNA probes, 75 koma kusanthula kwa data ya microarray kumatenga nthawi.
Kuzungulira kwa miR-122 ndi Let-7 kwanenedwa kukhala kothandiza pozindikira HCC yoyambilira m'magulu omwe ali pachiwopsezo chachikulu, zolembera odwala omwe ali ndi ma premalignant nodule okhudzana ndi HBV komanso HCC yoyambirira.76 Cai et al.adapeza kuti mamembala a banja la Let-7 (miR-92, miR-122, miR-125b, miR-143, miR-192, miR-16, miR-126, ndi miR-199a/b) ali pachiwopsezo chokhala ndi matenda osachiritsika. HCC kwa odwala matenda a chiwindi.Banja la Let-7 litha kukhala ngati biomarker yogwira ntchito yolosera za chitukuko cha HCC m'magulu omwe ali pachiwopsezo chokhudzana ndi matenda amtundu wa hepatitis C. 77 miR-122 ali ndi kulondola kwakukulu kwa matenda pozindikira HCC yoyambirira kwa odwala omwe ali ndi vuto la chiwindi.78 Serum yozungulira MiR-107 idawunikidwanso koyambirira kwa HCC, 79 ndipo yawonetsa kuthekera kwabwino kwa anthu omwe ali pachiwopsezo chachikulu.Zhou et al adanenanso kuti gulu la miRNAs (miR-122, miR-192, miR-21, miR-223, miR-26a, miR-27a ndi miR-801) limatha kusiyanitsa HCC ndi matenda a chiwindi a B (CHB) ndi cirrhosis. kukhudzika kunali 79.1% ndi 75%, ndi zenizeni 76.4% ndi 91.1%, motero.80 Mu HCC yokhudzana ndi HBV, tidapeza kuti miR150 milingo idachepetsedwa kwambiri poyerekeza ndi odwala omwe ali ndi HBV osatha omwe alibe HCC (sensitivity 79.1%, specificity 76.5%).-224 idakwezedwa mu HCC poyerekeza ndi maulamuliro athanzi, ndipo kusanthula kwamagulu ang'onoang'ono kunawonetsa milingo yayikulu kwa odwala omwe ali ndi HCC yokhudzana ndi HBV.hepatitis B-associated cirrhosis ndi odwala HCC adazindikira gulu la siRNA lomwe lili ndi ma siRNA asanu ndi awiri omwe amatha kuzindikira HCC mosiyanasiyana;Mitundu ya AUC pakuwunika koyambirira ndiyabwino kuposa odzipereka a AFP.Anapeza kuti ma miRNA anayi (miR-1972, miR-193a-5p, miR-214-3p, ndi miR-365a-3p) amatha kusiyanitsa odwala omwe ali ndi HCC ndi odwala opanda HCC.Ma miRNA asanu owonjezera (miR-122-5p, miR-125b-5p, miR-885-5p, miR-100-5p, ndi miR-148a-3p) amatengedwa kuti ndi matenda a HBV omwe angakhalepo mu HCC, cirrhosis, ndi CHB biomarkers, makamaka miR-34a-5p ikhoza kukhala zizindikiro za matenda a chiwindi,85 ndipo zikhoza kukhala zizindikiro zowunikira mwamsanga HCC m'magulu omwe ali pachiopsezo chachikulu.LncRNA yophunzira kwambiri mu HCC imayendetsedwa kwambiri mu khansa ya chiwindi (HULC).Kafukufuku wina wasonyeza kuti HULC yozungulira odwala HCC ingagwiritsidwe ntchito ngati chizindikiro cha matenda chifukwa lncRNA iyi imayendetsedwa kwambiri ndi odwala HCC poyerekeza ndi anthu athanzi.71,86 Pakati pa ma lnRNA ena, LINC00152 imatengedwa kuti ndiyo njira yabwino kwambiri yodziwira lncRNA chifukwa cha AUC yake yayikulu, kukhudzika kwake komanso kutsimikizika kwake.86 Mu kafukufuku wina, mawonekedwe a magazi a LINC00152 pang'onopang'ono adakula kuchokera kumayendedwe abwinobwino kwa odwala omwe ali ndi CHB ndi cirrhosis, ndipo pamapeto pake anali apamwamba kwambiri mu HCC.Kafukufuku wamafotokozedwe a circSMARCA5 m'madzi a m'magazi a odwala omwe ali ndi HCC awonetsa kuchepa kwapang'onopang'ono kwa mawu a HCC kuyambira pachiwopsezo cha chiwindi kupita ku cirrhosis ndi zotupa za precancerous.87 Kusanthula kwa ma curve a ROC kunatsimikizira kuthekera kwa ma circRNA awa posiyanitsa odwala omwe ali ndi matenda a chiwindi kapena chiwindi ndi omwe ali ndi HCC, makamaka omwe ali ndi ma AFP omwe ali pansi pa 200 ng/mL.Kuphatikiza apo, Zhu adasanthula ma 13,617 cyclic RNAs mu zitsanzo za plasma kuchokera kwa odwala HBV okhudzana ndi HCC ndipo adatsimikizira kuti 6 cyclic RNAs idawonetsedwa mosiyana mu HCC ndi HBV yokhudzana ndi cirrhosis, kutanthauza kuti cRNAs ikhoza kukhala yopindulitsa.zolembera zowunikira koyambirira kwa magulu omwe ali pachiwopsezo chachikulu monga omwe amakhudzidwa ndi matenda a chiwindi, odwala sclerosis.88
Exosomes ndi nembanemba vesicles 40-160 nm awiri;ma vesicles angapo a intracellular amalumikizana ndi nembanemba ya cell ndipo amatulutsidwa mu matrix a extracellular.Zili ndi zigawo zambiri zogwira ntchito, kuphatikizapo lipids, mapuloteni, RNA ndi DNA, ndipo zimagwira ntchito yofunika kwambiri poyankhulana pakati pa maselo, onse a HCC ndi omwe si a HCC.89,90 Exosomes imayang'anira kupititsa patsogolo kwa HCC mwa kuyambitsa hepatocyte fibroblasts ndi maselo a stellate, maselo a chitetezo cha mthupi, hepatocytes wamba, ndi maselo a HCC.91 Mu microenvironment chotupa, maselo otupa amatulutsa zotulutsa zambiri zomwe zimatengedwa kuchokera ku maselo a khansa kupita ku maselo osakhwima, omwe nawonso amakhudzidwa ndi oncogenesis, kuwonongeka, ndi ma signing a ma cell.92 Kafukufuku wawonetsa kuti ma exosomes amatha kusamutsa ma oncogenes kupita ku maselo abwinobwino panthawi ya pathological, yomwe ingakhale imodzi mwamakina a chotupa ndi metastasis.93 Udindo wa exosomes pakukula kwa khansara ukhoza kukhala wamphamvu komanso wokhudzana ndi mtundu wa khansa, 89 Exosomes akhoza kulowetsedwa mkati ndi maselo oyandikana nawo kapena akutali kuti athe kuwongolera majini angapo omwe amawalandira m'maselo omwe amalandira omwe angakhale nawo mu ma ions olankhulana ndi ma cellular ndi ma cellular microenvironment. kuwongolera ma sign a cell ndi metabolism.94 Makhalidwe ndi kusintha kwamphamvu kwa mamolekyu amtundu wa exosome amawonetsa mwachindunji mawonekedwe ndi kusintha kwamphamvu kwa maselo a chotupa cha makolo,95 omwenso ndi maziko ogwiritsira ntchito ma exosomes pozindikira ndi kuzindikira za khansa, komanso kulosera momwe munthu angayankhire chithandizo chamankhwala choletsa khansa. ..96
Njira zama laboratory zachikhalidwe zodzipatula ndi kusanthula ma exosomes ndizovuta, masitepe ambiri, komanso nthawi yambiri, kuphatikizapo ultracentrifugation, kusefera, kukula kwa chromatography, immunoaffinity purification, Western blotting, enzyme-linked immunosorbent assay (ELISA), PCR, ndi kusanthula koyenda.makina ang'onoang'ono ndi mapulaneti a lab-on-a-chip omwe amagwiritsa ntchito micro/nanotechnology akupangidwa mochuluka kuti azitha kudzipatula mwachangu komanso momasuka.Nanoparticle tracking analysis (NTA) ndi njira yomwe imagwiritsidwa ntchito kwambiri pozindikiritsa kukula ndi kuchuluka kwa ma exosomes, kuphatikiza njira monga maginito nanoparticles ndi polyhydroxyalkanoates.Njira za Microfluidic ndi electrochemical zimathanso kuzindikira mwachangu ma exosomes pazokolola zambiri.
Mapuloteni a Exosomal ndi ofunikira pakuzindikiritsa HCC.Mu kafukufuku wa Arbelaiz, mlingo wa 98 RasGAP SH3 womanga mapuloteni (G3BP) ndi polymeric immunoglobulin receptor (PIGR) unali wokwezeka kwambiri mu ma exosomes opangidwa ndi HCC, ndipo kuphatikizika kophatikizana kwa mapuloteni awiriwa kunali kopambana kuposa AFP.Kuchulukitsitsa kwachitsulo ndi chinthu chofunikira chomwe chimathandizira kukulitsa kwa HCC.Tseng adanenanso kuti hepcidin ikhoza kukhala ndi gawo lalikulu pakukana HCC.99 Exosomes yochokera ku sera ya odwala a HCC anali ndi chiwerengero chokwera kwambiri cha mitundu ya hepcidin mRNA kuposa anzawo athanzi, kutanthauza kuti hepcidin ikhoza kukhala chidziwitso chambiri cha HCC.Mapuloteni a 14-3-3ζ mu exosomes opangidwa ndi 100 HCC amatha kuchepetsa kuyambika kwa T cell, kuchulukana, ndi kusiyanitsa ndipo angapangitse kusintha kwa T cell kukhala ma T olamulira, zomwe zimapangitsa kuti T cell iwonongeke.101 Izi zimathandizidwa ndi kafukufuku wambiri wofufuza kuthawa kwa chotupa kuchokera pakuwunika kwa chitetezo chamthupi, 102 zomwe zingapangitse HCC tumorigenesis.
Kuphatikiza pa kukhalapo kwa ecRNA mu plasma kapena seramu, ma exosomes opangidwa ndi RNA amatha kugwiritsidwa ntchito poyang'ana nthawi yeniyeni poyang'ana chotupa ndikuzindikira kusintha kwa chotupa ndi kuyankhidwa kwa chithandizo.Mlingo wa exosomal miRNA-21 mu seramu yamagazi mu gulu la HCC unali wokwera nthawi 2.21 kuposa gulu la CHB, ndipo mu gulu la HCC linali lokwera nthawi 5.57 kuposa anthu athanzi.Mu kafukufuku wa Wang, ma exosomes adachulukitsa kwambiri HCC poyerekeza ndi odwala matenda a cirrhotic omwe ali ndi AUC ya 0.83 (95% CI 0.74-0.93) ndi 0.94 (95% CI 0.88-1.00).104 Deta yomwe idapezedwa idawunikira kukhudzidwa kwa mamolekyu ena onyamula katundu omwe amapitilira mulingo wa oncogenesis ndi kupita patsogolo kwa HCC.105 Seramu ya miR-221, miR-103, miR-181c, miR-181a, miR-93 ndi miR-26a imagwirizana.ndi metastasis, ndi miR21 milingo inali yochuluka kwambiri mwa odwala HCC kusiyana ndi olamulira athanzi komanso odwala CHB.102 LncRNA inali ndi phindu lachidziwitso mu HCC.Kafukufuku wasonyeza kuti exosomes yochokera ku sera ya HCC odwala ali ndi milingo yapamwamba kwambiri ya LINC00161, LINC000635, ndi lncRNA yoyendetsedwa ndi kusintha kukula kwa chinthu-β kusiyana ndi odwala opanda HCC, ndipo ma lncRNAs amagwirizanitsidwa kwambiri ndi TNM siteji ndi kuchuluka kwa chotupa.110 Conigliaro et al.Ma CD90 + exosomes adapezeka kuti akuwonetsa kuchuluka kwa lncRNAH19, yomwe idakulitsa kwambiri kutulutsidwa kwa vascular endothelial growth factor (VEGF) ndi VEGF-R1 receptor kupanga, potero kulimbikitsa angiogenesis.93 CircRNAs ndi mtundu wina wa exosomal ncRNAs - wofotokozedwa m'magulu otsika koma okhazikika pamitundu yonse ya zamoyo, ma circRNAs amasonyezanso tsatanetsatane wa mtundu wa selo, mtundu wa minofu, siteji yachitukuko, ndi ntchito zoyendetsera ntchito.111 circRNAs ndi zowunikira zowunikira khansa yoyambirira komanso yocheperako.112 Mayesero aposachedwa azachipatala awonetsa kuti kutsimikizika kwa ma miRNA pawokha polosera HCC sikwabwino.Chifukwa chake, kuzindikira kovutirapo pogwiritsa ntchito mayeso angapo (mwachitsanzo, miR-122 ndi miR-48a kuphatikiza ndi AFP) kungapangitse kuzindikira kwa HCC yoyambirira komanso kusiyanitsa kwa HCC ku cirrhosis.100
Odwala omwe ali ndi CHB ndi matenda a chiwindi ndi gulu lomwe limakhala pachiwopsezo chachikulu chopanga HCC.Kwa magulu omwe ali pachiwopsezo chachikulu, pokhapokha kuyankha kokhazikika kwa virological kukwaniritsidwa, njira yowunikira yotsika mtengo yotengera chiopsezo cha HCC iyenera kukhazikitsidwa, ndipo kuyezetsa koyambirira ndikofunikira pakuwongolera matenda ndi chithandizo cha HCC ndi chiŵerengero chapamwamba cha mtengo wapatali2. ..Njira zodziwira khansara koyambirira zili ndi malire ambiri: njira zoyezera msanga za khansa sizinapangidwe, ndipo kutsata nthawi zambiri kumakhala kochepa.Poyerekeza ndi njira zakale zowunikira, ukadaulo wa biopsy wamadzimadzi uli ndi zabwino zodziwikiratu: kumasuka kwa zitsanzo, kuzindikira kwa panrac, kubwezeredwa kwachitsanzo chabwino, komanso kuyankha mogwira mtima ku heterogeneity ya chotupa.Chifukwa cha kukwera mtengo kwa njira zolumikizidwa ndi biopsy yamadzimadzi, kugwiritsa ntchito kwawo pakuwunika kwa HCC sikunayesedwe mwachizolowezi.Ngakhale kupita patsogolo kwa kuzindikira kolondola pamlingo wa maselo, biopsy yamadzimadzi ndiyokwera mtengo kuti izindikire HCC mwa odwala omwe akufuna, ndikuchepetsa kugwiritsidwa ntchito kwake poyerekeza ndi njira zojambulira monga ultrasound ndi maginito maginito.113,114 Komabe, kafukufuku wam'mbuyomu adawonetsa kuti biopsy yamadzimadzi idawonetsa phindu lalikulu potengera zaka zosinthidwa bwino za moyo (QALYs).115 Ubwino wa biopsy yamadzi mu carcinoma yoyambirira ya m'mimba ndi nasopharynx yawonetsedwanso.116,117 Maonedwe apano ndikuti biopsy yamadzi imatha kuthandizira ma seramu biomarkers ndi kuwunika kwa radiological pakuzindikira ndi kuzindikira zotupa.117 118
Malinga ndi zolemba zamakono, ukadaulo wa biopsy wamadzimadzi wawonetsa chidwi kwambiri komanso kutsimikizika pakuwunika koyambirira kwamagulu omwe ali pachiwopsezo chachikulu cha khansa ya chiwindi.Mosasamala mtundu wa biopsy yamadzimadzi, imatha kusiyanitsa HCC ndi anthu omwe ali pachiwopsezo chachikulu opanda HCC, kutanthauza kufunikira kowunika koyambirira chifukwa kusiyana pakati pa anthu omwe ali pachiwopsezo chachikulu komanso athanzi kumawonekera.ctDNA ili ndi theka la moyo waufupi ndipo ingagwiritsidwe ntchito kuti izindikire HCC, kotero kusintha kulikonse kwa cDNA yochokera ku chotupa kungapereke umboni weniweni weniweni wa kukula kwa chotupa, makamaka kwa zotupa zazing'ono.Kuchuluka kwa ctDNA kumawonetsa kukula ndi kufalikira kwa khansa ndipo ndi chizindikiro choyambirira cha kupita patsogolo ndi kuyambiranso.Kuphatikiza apo, potengera zotsatira za ctDNA, odwala amatha kulandira chithandizo payekhapayekha ndikutsata.119 Malo enieni a methylation atha kukhala cholembera bwino kuposa AFP pozindikiritsa msanga HCC ndi ma cirrhotic nodule.Muzochitika zosinthika za HCC, kuchuluka kwa cDNA kumawonetsa kuwukira kwa ma microvascular and postoperative recurrence and metastasis.Kusintha kwa nambala yamakope kumalumikizidwa ndi kupulumuka kwa odwala omwe ali ndi HCC.Zitha kuganiziridwa kuti kuwunika kwa cDNA kungakhudzidwe ndi chithandizo chonse cha HCC, ndipo cDNA ikhoza kukhala chizindikiro chothandizira kusintha kwachirengedwe.Zolemba zotengera kusintha kwa majini mu ctDNA zatengedwa ndi malangizo azachipatala kuti athe kulosera momwe angagwiritsire ntchito bwino ndikuwunika kukana kwa mankhwala.Kuyesa kwa ctDNA kungakhale chida chothandiza kwambiri chamadzimadzi cha biopsy pakuwunika koyambirira.Ma CTC amakhalanso ndi gawo lalikulu pakuwunika koyambirira kwa magulu omwe ali pachiwopsezo chachikulu cha HCC.Zizindikiro zosiyanasiyana za ma CTC ogwirizana ndi HCC ndizofunikira kwambiri pakuyamba, kukula, ndi kubwereza kwa HCC.Monga ma membrane vesicles, ma exosomes amakhudzidwa ndi kulumikizana kwapakati, makamaka m'maselo a HCC.Ma microRNA ozungulira amakhala okhazikika m'magazi ndipo motero atha kukhala othandiza pakuwunika msanga kwa HCC.Pang'onopang'ono, mapuloteni a exosomal ndi ma exosome olemera a RNA adapezeka, ndipo mphamvu zawo zolosera za HCC zidatsimikiziridwa.Chosangalatsa ndichakuti, ma etiologies osiyanasiyana a HCC amathanso kulumikizidwa ndi masinthidwe osiyanasiyana, kotero titha kusankha ma biomarker osiyanasiyana kuti awonedwe koyambirira kutengera ma etiologies osiyanasiyana a HCC.120
Komabe, njira zaposachedwa za biopsy yamadzimadzi ndizokayikitsa pankhani yokhazikika ndipo sizingadziwike pawokha kapena kuwunika msanga HCC, komabe zimatha kuthandizana pakuwunika ndi kuzindikira.121 Monga mtundu wa biopsy yamadzi, kuzindikira ndi kujambula kwa ctDNA, CTC, cfRNA ndi AFP yogwirizana ndi exosome kapena PIVKA-II ali ndi ntchito zodalirika pakuzindikira koyambirira komanso kuzindikirika kwa HCC.Komabe, njira yeniyeni yotulutsira ctDNA m'magazi ikadali yodziwika.Kuwulula zofunikira zachilengedwe za ctDNA zitha kuthandizira kugwiritsidwa ntchito kwake ngati cholembera.Kachulukidwe kakang'ono ka ctDNA kakufalikira komanso zofunikira pakuwongolera zitsanzo ndizovuta pakukhazikitsa kwachipatala kwa cDNA kuzindikira mu HCC.Kuphatikiza apo, kusintha kwa ma genetic kulibe mawonekedwe enieni omwe amalola kuzindikirika kolondola kwa ma carcinogens.Popeza mitundu ingapo ya ma genetic ndi somatic iliponso m'magulu abwinobwino, kusintha kwa majini komwe kumadziwika ndi madzimadzi a biopsy kungakhale kothandiza pakuwunika koyambirira kwa HCC.122 Zolepheretsa za jini zomwe zimafotokozedwa bwino ndi zolembera zomwe zimathandiza kusiyanitsa cDNA kuchokera ku DNA yopanda chotupa ndi nkhani zofunika kwambiri pakugwiritsa ntchito cDNA.kusowa kothandiza kwa zolembera zodziwikiratu komanso zodziwika bwino pozindikira ma CTC.Maselo otheka okha omwe ali ndi kuthekera kwa metastatic adapezeka, ndipo kuphatikiza koyenera kwa zolembera za CSC kunali kosadziwika bwino.Kudzipatula kwa CTC pa chikhalidwe ndikuwunika mbiri yawo yosinthika ndi ntchito yovuta.Chifukwa cha mavuto ndi chizindikiritso, kudzipatula ndi kuyeretsedwa kwa exosomes, yeniyeni maselo limagwirira akadali osadziwika bwino, ndipo maphunziro m'mbuyomu pa limagwirira exosomes ndi HCC sizinakhale mozama, ndi mmene miRNAs, lncRNAs, ndi mapuloteni osanjidwa mu exosomes. , ndipo sizikudziwikiratu ngati kutengeka kwa exosome ndi njira inayake.Kugwiritsiridwa ntchito kwa exosomes pozindikira ndi kuchiza HCC kudakali pa preclinical siteji.Kusakhazikika kwa njira zamadzimadzi za biopsy, monga mtundu wa machubu omwe amagwiritsidwa ntchito kutengera magazi, kuchuluka kwa magazi, kusungirako zitsanzo ndi kuzindikira, kudzipatula ndi kulemeretsa, kungalepheretse kugwiritsidwa ntchito kwawo muzochita zachipatala chifukwa cha kusiyana kwa machitidwe m'zipatala.Kuchita bwino kwa biopsy yamadzimadzi pakuwunika koyambirira, kuzindikira, kuyesa mphamvu, komanso kuneneratu za HCC kukadali kufufuzidwa, makamaka kwamagulu omwe ali pachiwopsezo chachikulu.Tekinoloje ya Liquid biopsy ili ndi kuthekera kwakukulu ndipo ikuyembekezeka kugwiritsidwa ntchito kwambiri muzachipatala cha khansa ya chiwindi posachedwa.
1. Sung H., Furley J., Siegel RL et al.Global Cancer Statistics 2020: GLOBOCAN ikuyerekeza kuchuluka ndi kufa kwa mitundu 36 ya khansa m'maiko 185.CA Cancer J Clin.2021; 71(3):209-249.doi: 10.3322/caac.21660
2. Likulu la National Health Commission.Zofunikira pakuzindikiritsa ndi kuchiza khansa yachiwindi yayikulu (kope la 2022) [J].Journal of Clinical Chiwindi Matenda, 2022, 38 (2): 288-303.doi: 10.3969/j.issn.1001-5256.2022.02.009
3. Zhou J, Sun H, Wang Z, et al.Malangizo ozindikira ndi kuchiza hepatocellular carcinoma (kope la 2019).Khansa ya chiwindi.2020; 9(6): 682-720.doi: 10.1159/000509424
4. Kokudo N, Takemura N, Hasegawa K, et al.Malangizo azachipatala a hepatocellular carcinoma: Japanese Society for Liver Diseases, 2017 (JSH-HCC 4th guidelines), 2019 update.Malo osungira Matenda a Chiwindi.2019;49(10):1109–1113.doi:10.1111/hepr.13411
5. Barrera-Saldana HA, Fernandez-Garza LE, Barrera-Barrera SA Liquid biopsy mu matenda aakulu a chiwindi.Ann Hepato.2021; 20:100197.doi:10.1016/j.aohep.2020.03.008
6. Tai TKYu., Tan P.Kh.Liquid khansa ya m'mawere biopsy: ndemanga yolunjika.Arch Pathol Lab Med.2021; 145 (6): 678-686.doi: 10.5858/arpa.2019-0559-RA
7. Kanval F., Singal AG Kuwunika kwa hepatocellular carcinoma: machitidwe abwino amakono ndi malangizo amtsogolo.Gastroenterology.2019; 157(1):54-64.doi:10.1053/j.gastro.2019.02.049
8. European Research Association L, European Organization R, C Therapeutics.Malangizo azachipatala EASL-EORTC: chithandizo cha hepatocellular carcinoma.J Heparin.2012; 56 (4): 908-943.doi:10.1016/j.jhep.2011.12.001
9. Zhang G., Ha SA, Kim HK et al.Kusanthula kophatikizana kwa AFP ndi HCCR-1 ngati zolembera zothandiza za serological mu carcinoma yaying'ono ya hepatocellular: kafukufuku wamagulu omwe akuyembekezeka.Ndi Mark.2012; 32 (4): 265-271.doi: 10.3233/DMA-2011-0878
10. Chen S, Chen H, Gao S, et al.Kusiyanitsa kwa plasma microRNA-125b mu matenda a chiwindi a hepatitis B okhudzana ndi kachilombo ka HIV komanso kuthekera kwa matenda a hepatitis B omwe amachititsa kuti pakhale hepatocellular carcinoma.Malo osungira matenda a chiwindi.2017;47(4):312-320.doi:10.1111/hepr.12739
11. Halle PR, Foster F., Kudo M. et al.Biology ndi kufunika kwa alpha-fetoprotein mu hepatocellular carcinoma.Chiwindi int.2019;39(12):2214–2229.doi: 10.1111/liv.14223
12. Omata M, Cheng AL, Kokudo N, et al.Malangizo azachipatala ochizira hepatocellular carcinoma m'chigawo cha Asia-Pacific: Kusintha kwa 2017.International Organisation for Chiwindi Diseases.2017; 11 (4): 317-370.doi: 10.1007/s12072-017-9799-9
13. Xu Fei, Zhang Li, He Wei et al.Kuzindikira kufunika kwa seramu PIVKA-II yokha kapena kuphatikiza ndi AFP kwa odwala aku China omwe ali ndi hepatocellular carcinoma.Ndi Mark.2021;2021:8868370.doi: 10.1155/2021/8868370
14. Durin L., Praradines A., Basset S. et al.Khansara ya m'mapapo yosakhala yaing'ono yopanda plasma humoral fluid biopsy: pafupi ndi chotupacho!selo.2020;9(11).doi: 10.3390/maselo9112486
15. Mader S, Pantel K. Liquid biopsy: mkhalidwe wamakono ndi ziyembekezo zamtsogolo.Chithandizo cha Oncol Res.2017;40(7-8):404-408.doi: 10.1159/000478018
16. Palmirotta R, Lovero D, Cafforio P, et al.Liquid-based cancer biopsy: chida chowunikira ma multimodal mu chipatala oncology.Adv Med Oncol.2018;10:1758835918794630.doi: 10.1177/1758835918794630
17. Mandel P., Metais P. Nucleic acids mu plasma yaumunthu.CR Seances Soc Biol Fil.1948;142(3-4):241-243.
18. Mouliere F, Chandrananda D, Piskorz AM, et al.Kuzindikira kwapamwamba kwa chotupa cha DNA chozungulira pofufuza kukula kwa zidutswa.Sayansi imamasulira mankhwala.2018; 10:466.doi:10.1126/scitranslmed.aat4921
19. Underhill HR, Kitzman JO, Hellwig C. et al.Kuzungulira chotupa DNA fragment kutalika.Mitundu ya PLOS.2016;12(7):e1006162.doi:10.1371/journal.pgen.1006162
20. Cheng F, Su L, Qian C. Kuzungulira chotupa cha DNA: chizindikiro chodalirika mu biopsy ya khansa yamadzimadzi.chotupa chandamale.2016;7(30):48832–48841.doi:10.18632/oncotarget.9453
21. Bettegovda S., Sauzen M., Leary RJ et al.Kuzindikira kwa chotupa cha DNA chozungulira koyambirira komanso mochedwa kwa zilonda zamunthu.Sayansi imamasulira mankhwala.2014;6(224):224ra24.doi:10.1126/scitranslmed.3007094
22. Mehes G. Liquid biopsy for mutational predictive analysis of solid cancer: kaonedwe ka katswiri wa matenda.J Biotechnology.2019; 297:66-70.doi: 10.1016/j.jbiotec.2019.04.002
[PubMed] 23. Lenarts L, Tuveri S, Yatsenko T, et al.Kuzindikira koyambirira kwa chotupa pozungulira kuwunika kwa DNA ya plasma: hype kapena chiyembekezo?Lamulo lachipatala la Belgium.2020;75 (1):9-1 doi:10.1080/17843286.2019.1671653
24. Nishida N. Zotsatira za kachilombo ka hepatitis ndi ukalamba pa DNA methylation mu human hepatocarcinogenesis.Histopathology.2010;25(5):647–654.doi: 10.14670/HH-25.647