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Ding Jingnuo, Zhao Weifeng, Ishami ry’indwara zandura, Ibitaro bya mbere bya kaminuza ya Suzhou, Umujyi wa Suzhou, Intara ya Jiangsu, 215000 Tel.ibibyimba bya sisitemu yumubiri hamwe nimyaka 5 muri rusange kubaho 14.1%.Abarwayi benshi barwaye HCC basuzumwa mugihe cyateye imbere, bityo kwisuzumisha hakiri kare ni ngombwa kugabanya impfu ziterwa na HCC.Usibye ibipimo bisanzwe bikoreshwa mugushakisha nka serumu alpha-fetoprotein (AFP), lens lectin-reactive alpha-fetoprotein (AFP-L3), hamwe na prothrombine idasanzwe (vitamine K ibura vitamine K iterwa na poroteyine II, PIVKA-II), tekinike ya biopsy fluid Byerekanwe ko bifite agaciro ko gusuzuma mugushakisha HCC.Ugereranije nuburyo butera, biopsy fluid irashobora gutahura metabolite mbi.Tekinike ya biopsy ya flux itahura ingirabuzimafatizo yibibyimba, kuzenguruka ibibyimba ADN, kuzenguruka RNA, na exosomes kandi bikoreshwa mugupima hakiri kare, gusuzuma, no gusuzuma progaramu ya HCC.Iyi ngingo isubiramo ibinyabuzima bya molekuline no gukoresha uburyo butandukanye bwa biopsy ya fluid kugirango itandukanya biomarkers itanga ibyiringiro bishobora kuba amahitamo meza yo gusuzuma hakiri kare HCC kugirango tunonosore hakiri kare amatsinda ya HCC afite ibyago byinshi.Ijambo ryibanze: tekiniki ya biopsy tekinike, kanseri ya hepatocellular, itsinda rishobora kwibasirwa cyane.
Kanseri ya Hepatocellular (HCC) ni ikibyimba gikunze kwibasira inzira y'igifu, kiza ku mwanya wa gatandatu mu bantu bashya banduye ibibyimba bibi ku bagabo no ku bagore.1 Kw'isi yose, kanseri y'umwijima niyo mpamvu ya gatatu itera kanseri y'urupfu nyuma ya kanseri y'ibihaha na kanseri y'urura runini, bingana na 8.3% by'impfu ziterwa na kanseri ziterwa na neoplasme mbi.1 Kumenyekanisha HCC bifitanye isano rya bugufi nicyiciro cyo gusuzuma.Impamvu nyamukuru zitera kubaho nabi muri HCC ni metastase methease, portal venous tumor trombi, hamwe na metastase ya kure ibuza kwanga, kandi ibyinshi muribyo biranga abarwayi mugihe cyo kwisuzumisha.
Hashingiwe ku mabwiriza yo gusuzuma no kuvura, ibintu nyamukuru bishobora gutera HCC ni cirrhose y'umwijima, virusi ya hepatite B idakira (HBV) cyangwa virusi ya hepatite C (HCV), indwara y’umwijima y’umwijima, n’indwara y’umwijima idafite inzoga (NAFLD) ).2 Byongeye kandi, ibintu bishobora gutera HCC harimo gufata ibiryo byanduye aflatoxine, schistosomiasis, izindi mpamvu zitera cirrhose, amateka yumuryango wa kanseri yumwijima, diyabete, umubyibuho ukabije, kunywa itabi, no gukomeretsa umwijima biterwa numwijima.Amatsinda afite ibyago byinshi byimyaka 35 na 45 agomba kwisuzumisha buri gihe.Kwipimisha hakiri kare ningamba zingenzi zo kuvura hakiri kare kugirango ubuzima rusange bwabarwayi barwaye HCC.
Ibinyabuzima nka AFP, AFP-L3 na PIVKA-II birasabwa kwipimisha hakiri kare HCC3,4.Tekinike ya biopsy yubuhanga yerekanye ibisubizo bitanga umusaruro mugupima hakiri kare no gusuzuma imiti.5,6 Intambwe igaragara imaze guterwa muri biopsy ya HCC, ishobora kuba ifite sensibilité kandi yihariye kuruta ibimenyetso bya serumu bisanzwe bikoreshwa nka AFP (Imbonerahamwe 1).
AFP ni biomarker ikoreshwa cyane muri HCC kandi kuri ubu ni biomarker irambuye ikoreshwa cyane mugupima hakiri kare, gusuzuma, no gusuzuma indwara.Urwego rwa AFP rwakomeje kuzamuka bifatwa nkimpamvu zishobora gutera iterambere rya HCC.7,8 Igipimo cyo gutahura kanseri ntoya ya hepatocellular (sHCC) kiriyongera hamwe niterambere rya ultrasound na computing tomografiya, kandi AFP byagaragaye ko itumva cyane cyane kumenya HHCC mubikorwa byubuvuzi.Ubushakashatsi bwakozwe na retrospective multicentre9 bwerekana ko icyiza cya AFP cyagaragaye muri 46% (616/1338) mu manza za HCC na 23.4% (150/641) z’imanza za sHCC.Byongeye kandi, urwego rwa AFP rwazamutse ku barwayi bafite umwijima udakira na cirrhose.10 Rero, AFP ifite ingaruka nke zo gusuzuma kuri sHCC.11 Dukurikije amabwiriza ngenderwaho y’ubuvuzi bwa Aziya-Pasifika ya Hepatocellular Carcinoma, ntabwo byemewe gukoresha AFP.12 Ibimenyetso by’amavuriro byerekana ko PIVKA-II iruta AFP mu kuvura HCC kandi ko guhuza PIVKA-II na AFP bifite agaciro gakomeye ko kwisuzumisha muri HCC.13 Ugereranije na biopsy ya tissue, biopsy fluid yibanda cyane cyane metabolite ijyanye nibibyimba mumazi yumubiri (maraso, amacandwe, fluid pleural fluid, cerebrospinal fluid, cyangwa inkari) kandi ntishobora kwibasira imyenda.14 Byongeye kandi, biopies yamazi irashobora kwerekana ibintu bibi bitagaragara mubice byambere byibibyimba.15 Amazi ya biopies ntabwo arageragezwa mubikorwa byubuvuzi bwubwoko bwose bwibibyimba, ariko ubushobozi bwabo bwo gupima kanseri burimo gukurura ibitekerezo bya oncologiste.16 Fluid biopsy irashobora gutahura ingirabuzimafatizo zibyimba (CTCs), kuzenguruka ibibyimba ADN (cDNA), kuzenguruka RNA yubusa (ecRNA), na exosomes.Muri iki kiganiro, tuzaganira kubiranga, uruhare, nuburyo bukoreshwa muburyo butandukanye bwamazi ya biopsy mugusuzuma hakiri kare amatsinda ya HCC afite ibyago byinshi.
ADN idasanzwe (cfDNA) mu maraso yatanzwe n'abantu bafite ubuzima bwiza yasobanuwe bwa mbere mu 1948 na Mandel n'abandi.17 cfDNA ni ADN idafite selile igizwe na ADN hafi 160-180 bp z'uburebure, ikomoka ahanini kuri lymphocytes na selile myeloid.ctDNA ni agace kihariye ka ADN ya mutant irekurwa na selile yibibyimba mumaraso ya periferique, igereranya amakuru ya genomic ya selile yibibyimba nyuma yuburyo bumwe na bumwe bwa patrophysiologique, harimo na nérosose, apoptose, no gusohoka.Umubare wa ctDNA muri cfDNA yose uratandukanye cyane nubwoko bwibibyimba, kandi ibice bya cDNA bivugwa mubisanzwe bitarenze 167 bp muburebure.18 Ubushakashatsi bwakozwe na Underhill bwerekanye ko ibice bya cfDNA muri rusange ari bigufi kuruta cfDNA isanzwe.19 Ugereranije n’abantu bafite ubuzima bwiza, uburebure bwa cfDNA mu maraso y’abarwayi ba kanseri ni bugufi, bityo cfDNA irashobora gukoreshwa nk'ikimenyetso cyo gusuzuma ibibyimba hakiri kare.Gutunganyiriza uduce tumwe na tumwe twuburebure bwa cfDNA birashobora kunoza kumenya cDNA ifitanye isano nibibyimba bikomeye bitari metastatike.Ubushakashatsi bwerekanye ko ctDNA iboneka hejuru ya 75% ya pancreatic, colon, uruhago, gastrointestinal, umwijima, ovarian, amabere, melanoma, na kanseri yo mumutwe no mu ijosi.20,21 Ariko, ingano ya ctDNA mumaraso iterwa nigihe ikibyimba giherereye.22 Mu bushakashatsi bwakozwe na Bettegoud, abarwayi bafite kanseri yibara, amabere, umwijima, ibihaha, na prostate basanze bafite cDNA nyinshi mu maraso yabo kurusha izindi kanseri.Ibinyuranye n'ibyo, ku barwayi barwaye kanseri yo mu kanwa, kanseri yandura, kanseri yo mu gifu, na glioma, cDNA yibanze mu maraso yari hasi.makumyabiri na rimwe
Kuberako ctDNA ikubiyemo ihindagurika ryimiterere nki ngirabuzimafatizo yibanze, cDNA irashobora gukoreshwa mugutahura ihinduka ryimiterere yihariye yibibyimba ndetse nimpinduka za epigenetike, harimo methylation, hydroxymethylation, nucleotide imwe, hamwe na kopi zitandukanye.makumyabiri na gatatu
Methylation ya ADN ni imwe mu mpinduka zikunze kugaragara zikaviramo guhashya gene.Ugereranije na selile zisanzwe, hariho itandukaniro murwego rusange rwa methylation ya genom selile yibibyimba, cyane cyane muri methylation ya genes suppressor genes, ishobora kugaragara hakiri kare, byerekana ko impinduka za methylation ya ADN zishobora kuba ikimenyetso cya kare gutahura tumorigenez.Tumor suppressor genes ifitanye isano na HCC irashobora kudakorwa na methylation ya promoter, bityo igatera tumorigenez.Methylation ya ADN ni ikimenyetso cyiza cyo gusuzuma hakiri kare ibibyimba bitewe nimiterere yacyo, kumenyekana, no kwigenga kwimyaka.Byongeye kandi, methylation ya ADN ikunze kugaragara ugereranije na mutation ya somatike kuko hari uturere twinshi twerekanwe hamwe na CpG nyinshi zahinduwe muri buri karere ka genome yagenewe.25 Usibye imbuga nyinshi za CpG, umubare munini wigenga wa hypermethylated loci muri ctDNA wagaragaye muri DBX2, THY1, MT1M, INK4A, VIM, FBLN1, na RGS10.26 Xu nibindi.Kugereranya ingero za cfDNA zivuye ku barwayi 1098 ba HCC na 835 igenzura ryiza ni genes zifitanye isano na HCC wasangaga zifitanye isano rya bugufi na plasma cDNA methylation ihuye.25 Hashingiwe ku isesengura rya laboratoire, hashyizweho uburyo bwo guhanura burimo ibimenyetso 10 bya methylation bifite sensibilité kandi byihariye bya 85.7% na 94.3%, kandi ibyo bimenyetso byari bifitanye isano cyane n’ibibyimba, ikibyimba, hamwe n’uburyo bwo kuvura.Ibisubizo byerekana ko gukoresha ibimenyetso bya cDNA methylation bifite amasezerano akomeye mugupima, kugenzura, no gutangaza HCC.Mu buryo bwa methylation bugizwe na genes eshatu methylated (APC, COX2, RASSF1A) na miRNA imwe (miR203) yatanzwe na Lu et al27, ibyiyumvo byihariye hamwe nicyitegererezo cya 27 cyo gusuzuma HCC ifitanye isano na HCC.80%.Byongeye kandi, icyitegererezo gishobora kumenya 75% byabarwayi ba HCC batamenyekanye bafite urwego rwa AFP rwa 20 ng / mL.Gene kumuryango wa Ras ifitanye isano na poroteyine 1A (RASSF1A) ningenzi nyamukuru isubiramo ADN ikurikirana muri genomuntu.Araujo n'abandi.yanzuye ko hypermethylation ya porotokoro ya RASSF1A ishobora kuba biomarker yingirakamaro mugupima hakiri kare HCC hamwe nintego ya molekile ishobora kuvura epigenetike.28 Mu bushakashatsi bumwe, serumu RASSF1A promoter hypermethylation yabonetse muri 73.3% byabarwayi bafite HCC.29 Nucleotide ndende ihuza intera 1 (LINE-1) nundi muhuza ukora cyane retrotransposition.Hypomethylation ya LINE-1 yabonetse muri ADN ya 66.7% by'icyitegererezo cya serumu ya HCC kandi yari ifitanye isano no kugaruka hakiri kare no kubaho nabi nyuma yo kwangwa bikabije.29 Hypermethylation ni inzira rusange ya genetike igira uruhare rudasanzwe mugutezimbere umwijima cirrhose na HCC.30 Ibinyuranye na byo, hydroxymethylation ni inzira ya demethylation itera gene kongera gukora no kwerekana, kandi kumenya ibicuruzwa 5-hydroxymethylcytosine (5-hmC) muriki gikorwa birashobora gukoreshwa kugirango hamenyekane ikibyimba.Methylation na hydroxymethylation ya cDNA ifitanye isano na tumorigenez kandi irashobora kugira uruhare mugupima hakiri kare HCC.Mu bushakashatsi bwakozwe ku masomo 2554, 31 genome-5-hmCs yabonetse mu ngero za cfDNA, naho gen 32 zagaragaye ugereranije 5-hmC zikurikirana ku barwayi ba HCC hamwe n’itsinda ry’ibyago byinshi nk’abafite indwara zidakira.Uburyo bwo gusuzuma indwara zumwijima.na cirrhose.Iyi moderi yarutaga AFP mugutandukanya HCC nuduce twibibyimba.
Imihindagurikire y’akarere ka code irashobora gutuma habaho kwandura ibintu bidasanzwe, bishobora gutera impinduka za poroteyine hanyuma kanseri ikarangira.Impinduka imwe ya nucleotide ni ibimenyetso byingenzi byerekana ibimenyetso byerekana ibibyimba hakiri kare bitewe nubwizerwe bwabyo bwinshi hamwe nibibyimba byinshi hamwe na tissue yihariye.Ubushakashatsi bwinshi bujyanye na HCC bukoresheje ibisekuruza bizaza (NGS) kuri exome na genome zose zikurikirana za kanseri byagaragaje ingirabuzimafatizo rusange zahinduwe nka TP53 na CTNNB1, ndetse na nyinshi zirimo ARID1A, MLL, IRF2.Imirasire mishya, ATM, CDKN2A, FGF19, PIK3CA, RPS6KA3 na JAK1 yerekana igipimo cya mutation giciriritse. Isesengura ry'imikorere ya gene ryerekana ko impinduka muri chromatin ivugurura, Wnt / β-catenin na JAK / STAT ikwirakwiza ibimenyetso, inzira ya P53-selile cycle, inzira ya epigenetike, inzira ya oxydeide, inzira ya PI3K / AKT / MTOR n'inzira ya RAS / RAF / Inzira ya MAPK kinase igira uruhare runini muri oncogenezi ya HCC.32,33 Mu bushakashatsi bwagaragaye ko ihinduka ry’imihindagurikire y’ibibyimba ryagaragaye, Huang n'abandi basanze inshuro z’imihindagurikire y’ibibyimba biterwa na ctDNA yari 19.5%, kandi umwihariko ni 90% .34 Byongeye kandi, abarwayi bahuye nigitero cyamaraso wasangaga bafite ihinduka rya ctDNA (P = 0.041) hamwe nigihe gito cyo kubaho (P <0.001). Isesengura ry'imikorere ya gene ryerekana ko impinduka muri chromatin ivugurura, Wnt / β-catenin na JAK / STAT ikwirakwiza ibimenyetso, inzira ya P53-selile cycle, inzira ya epigenetike, inzira ya oxydeide, inzira ya PI3K / AKT / MTOR n'inzira ya RAS / RAF / Inzira ya MAPK kinase igira uruhare runini muri oncogenezi ya HCC.32,33 Mu bushakashatsi bwagaragaye ko ihinduka ry’imihindagurikire y’ibibyimba ryagaragaye, Huang n'abandi basanze inshuro z’imihindagurikire y’ibibyimba biterwa na ctDNA yari 19.5%, kandi umwihariko ni 90% .34 Byongeye kandi, abarwayi bahuye nigitero cyamaraso wasangaga bafite ihinduka rya ctDNA (P = 0.041) hamwe nigihe gito cyo kubaho (P <0.001).Isesengura ryimikorere ya mutant yerekana ko impinduka zoguhindura chromatin, Wnt / β-catenin na JAK / STAT byerekana, inzira ya P53 selile cycle, inzira ya epigenetike, inzira ya stress ya okiside, inzira ya PI3K / AKT / MTOR, hamwe na RAS / RAF / MAPK kinase inzira ikina uruhare runini muri HCC tumorigenez.32,33 Mu bushakashatsi bwerekanye ihinduka ry’imiterere ihindagurika, Huang n'abandi.wasanze inshuro ya ctDNA iterwa nibibyimba biterwa na mutation yari 19.5% naho umwihariko ni 90%..3 .34 Byongeye kandi, abarwayi batewe n'imitsi bafite ihinduka ryinshi rya cDNA (P = 0.041) hamwe no kubaho igihe gito kitarwaye indwara (P <0.001).Isesengura ryimikorere ya genes ya mutant ryerekanye chromatin ivugurura, Wnt / β-catenin na JAK / STAT ibimenyetso, inzira ya selile ya P53, inzira ya epigenetike, inzira ya oxydeide, inzira ya PI3K / AKT / MTOR, hamwe na RAS / RAF / MAPK inzira ya kinase igira uruhare runini muri oncogenezi ya HCC. 32,33 在 一项 检测 到 相关 ang ang ang ang ang ang ang ang ang ang ang ang ang ang t t t t t t t t t突变 （P = 0.041） 和 更 短 的 无 复发 生存 （P <0.001）。 32.33 在 一 项 检测 相关 突变 突变 u u u ang ang ang t t t t t t <的 无 复发 生存 期 （P <0.001）。32,33 Mu bushakashatsi bwerekanye ihinduka ry’imiterere ihindagurika, Huang n'abandi.basanze ihinduka ryimiterere yibibyimba ryatewe na 19.5% biterwa na cDNA ifite umwihariko wa 90% 34. Byongeye kandi, abarwayi bagabweho igitero cyamaraso bakunze kwandura cDNA.мута (P = 0,041) и более короткая стрецидивная выживаемость (P <0,001). mutation (P = 0.041) no kubaho igihe gito kitarwaye indwara (P <0.001).Ubundi gene ya HCC isanzwe ni TP53, ifite igipimo cya mutation irenga 30%.Ubushakashatsi bwerekanye ko inshuro za mutation ya TP53 muri ctDNA mumaraso ninkari ziri hagati ya 5% na 60%.35 Ubushakashatsi bwa Johan bwerekanye ko ctDNA ihindagurika ryimiterere ya nyuma ya HCC ifite igipimo gisa nki ihinduka rya HCC yo hambere, harimo na TERT promoter (51%), TP53 (32%), CTNNB1 (17%), PTEN (8%), ihinduka muri AXIN1., ARID2, KMT2D na TSC2 (6% buri umwe).36 β-catenin (CTNNB1) oncogene igira uruhare runini muri Wnt yerekana inzira.Coactivator ya transcription ya CTNNB1 irashobora guteza imbere imvugo ya gene, ishobora gutuma ikwirakwizwa ry'uturemangingo, kubuza apoptose, na angiogenez.CTNNB1 irashobora kandi gukorana na TERT kugirango itume hepatocyte ihinduka.33 Umujyanama wa TERT ahinduka kenshi mubibyimba bimwe bikomeye.Guhindura muri TERT, imwe mumpinduka zambere za genetike muguhindura nabi kwa HCC, birashobora gutuma telomerase yongera gukora muri hepatocytes ya cirrhotic kandi ishobora guteza imbere ikwirakwizwa no kwirinda gusaza.Guhinduka kwa 33-37 porotokoro ya TERT byavuzwe ko bigaragara kuri 59-90% byabarwayi bafite umwijima mwinshi wumwijima na HCC kare kandi bifitanye isano no kubaho.38
Gukoporora umubare uhinduka (CNA) ni ubwoko bwingenzi bwimiterere ihindagurika.Ubushakashatsi bwerekanye ko umutwaro ukabije wa CNA ari umukono wa genomique ushobora guhanura ibibyimba byinjira mu mubiri ndetse no guhezwa mu bwoko bumwe na bumwe bwa kanseri.39 Ibimenyetso bifatika byinjira, ibikorwa byinshi bya cytolytike, gutwika cyane hamwe nibimenyetso bya geneti bifitanye isano no kwerekana antigen muri HCC.Isesengura ryamakuru yamakuru ya nucleotide polymorphism imwe mu ngingo 477 yerekanye umutwaro muke kuri CNS.Ibinyuranye, ibibyimba bya chromosomale bidahindagurika bifite umutwaro munini wa CNA byerekanaga ibimenyetso byo kwanga ubudahangarwa kandi byajyanye no gukwirakwira, gusana ADN, no kudakora neza kwa TP53.Xu n'abandi.yerekanye ko itsinda rya HCC ryagize amanota menshi ya CNA kurusha itsinda ryindwara zidakira.40 Ukoresheje genome yose ikurikirana ya selile imwe, wasangaga CNAs igaragara hakiri kare muri hepatocarcinogenez kandi ikomeza kuba nziza mugihe ikibyimba kigenda gikura.41 Chung n'abandi.basanze urwego rwa cfDNA rwazamutse cyane ku barwayi ba HCC kandi ko CNAs zose zigizwe na genoside muri cfDNA ari ikimenyetso cyingenzi cyigenga mu barwayi ba HCC bavuwe na sorafenib.42 Abarwayi bafite umutwaro munini wa CNA wasangaga bafite uburwayi n'indwara kurusha abafite umutwaro muto wa CNA.Ollerich n'abandi.basanze kopi yimibare idahwitse (CNI) ishobora gukoreshwa mugusuzuma CNA muri cfDNA yabarwayi ba kanseri.Bagaragaje ko abarwayi ba kanseri yateye imbere bafite amanota menshi ya CNI kurusha itsinda rishinzwe kugenzura, risuzuma uko abarwayi bitabira imiti ya chimiotherapie na immunotherapi.43 Ibisubizo byerekana ko CNAs iboneka mu mazi ya biopsy y’amazi ishobora kuba ibimenyetso byerekana abarwayi bafite kanseri yateye imbere.HCC inyuma yubuvuzi bwa sisitemu.
Kugeza ubu, uburyo bukoreshwa mugutahura ctDNA burashobora kugabanwa muburyo bugenewe kandi butari intego.Muri make, uburyo bugamije nka sisitemu ya polymerase yerekana reaction (dPCR), BEAMING digital PCR, Amplification Refractory Mutation System-PCR, Capp-Seq na Tam-Seq byumva cyane genes zateganijwe mbere.Uburyo butari intego nkuburyo bukurikirana bwa genome hamwe na NGS bitanga ishusho yuzuye yimiterere rusange.Ugereranije na panne yibikoresho, genome ikurikirana ntishobora kumenya gusa ihinduka ryimiterere no kwinjiza, ariko kandi irashobora guhinduranya no gukoporora umubare.guhanura, na CTC na cfDNA nibipimo byiza bishobora gukoreshwa mugukurikirana imbaraga za HCC.45 Byongeye, isesengura rya cfDNA rishobora kuba ingirakamaro mugushakisha HCC.Yan n'abandi.yerekanye ko cfDNA muri plasma yabarwayi bafite HCC yari hejuru cyane ugereranije n’abarwayi bafite fiboside yumwijima no kugenzura neza.Ugereranije na AFP, ctDNA iteganijwe kuba ikimenyetso cyiza cyo gusuzuma mbere ya HCC.46 Mu bushakashatsi bwakorewe kuri biopies 47 y’amazi yapimishije cfDNA na proteyine mu baturage, bagaragaje ko ari ingirakamaro mu gutandukanya abarwayi bafite HCC n’abarwayi badafite HCC.Mu gukurikirana abarwayi ba ultrasound 331 basanzwe na AFP-mbi, ibyiyumvo byihariye na cfDNA yo gusuzuma HCC byari 100% na 94%, bityo cDNA yashoboraga kumenya HCC mubantu badafite ibimenyetso bya HBsAg.Mu bushakashatsi bwa Yeo48, inshuro nyinshi (92.5%) ya hypermethylation ya porotokoro ya RASSF1A yabonetse ku barwayi bafite HCC.Byongeye, Xu n'abandi.yashyizeho uburyo bwo gusuzuma bwo guhanura HCC ikoresheje akanama kerekana ibimenyetso bya methylation yihariye ifite umwihariko na sensibilité ya 90.5% na 83.3%.Itsinda ryemerera abarwayi bafite HCC gutandukana n’abarwayi bafite izindi ndwara z’umwijima, bikaba byiza kuruta AFP.Basanze kandi igenzura risanzwe ryipimishije ryiza rishobora kugira ingaruka kuri HCC, nk'ubwandu bwa HBV cyangwa amateka yo kunywa inzoga.25 Turakeka ko ibintu bishobora guteza ibyago byinshi kuri HCC bishobora guteza hypermethylation ya cfDNA, hanyuma bikagira uruhare mu iterambere rya HCC, bityo cfDNA ikagira uruhare runini mugusuzuma amatsinda afite ibyago byinshi.Cai n'abandi.vuga muri make urwego rwose rwa mutation ya ctDNA kandi utange ingamba zihamye zo gusuzuma uburemere bwibibyimba kubarwayi.49 Izi ngamba zirashobora kumenya tumorigenezi hagati yamezi 4,6 mbere yo kwerekana amashusho kandi yerekanye imikorere isuzumisha ugereranije na serumu biomarkers AFP, AFP-L3, na PIVKA-II.Agaciro ko kwisuzumisha kwa cDNA kwerekanwe mugihe isuzuma ryibishusho ridahari, bityo igeragezwa rya cDNA ningirakamaro mugupima HCC kare mumatsinda afite ibyago byinshi.Vuba aha, abahanga bifashishije ikoranabuhanga rya NGS mu gusesengura ibipimo byerekana itandukaniro rishingiye ku moko atandukanye (harimo 5-hydroxymethylcytosine, 5′-motif, gucamo ibice, nucleosome, HIFI) mu byitegererezo by’amavuriro 3204 na cfDNA.50 Yongeye kwemezwa na moderi ya HIFI hamwe na gari ya moshi eshatu zigenga, ibizamini, hamwe n’ibizamini byagaragaje ivangura rihamye kandi ryizewe hagati y’abaturage ba HCC n’abatari HCC bafite 95.79% na 95.42% byunvikana mu bizamini bya HCC byihariye.Igitsina cyari 95.00% na 97.83%.Agaciro ko gusuzuma uburyo bwa HIFI burenze ubwa AFP mugutandukanya HCC na cirrhose.Mubyongeyeho, ctDNA ikoreshwa no mubuvuzi bwo kubaga.Atsushi n'abandi.yagennye urugero rwa serumu mbere yo gutangira ctDNA kubarwayi barwaye HCC basanga igipimo cyisubiramo nigipimo cya metastasis zidasanzwe mu itsinda ryiza rya cDNA cyari hejuru cyane ugereranije n’itsinda ribi rya cDNA, kandi urwego rwa cDNA rwahujwe cyane.hamwe no kubyimba.51 Kuba biomarker yunvikana cyane, ctDNA irashobora guhanura ubushobozi bwa HCC gutera ubwato.Wang n'abandi.yakoze genome yose uko yakabaye abarwayi 46 barwaye HCC, kandi isesengura ryinshi ryerekanye ko agaciro ntarengwa ka allele inshuro nyinshi za cDNA yo gutera mikorobe ari 0.83%, sensibilité 89.7% kandi yihariye 80.0%.ibintu byigenga bishobora gutera microcasculaire yibasirwa na HCC, byerekana ko cDNA ishobora gufasha kuvura neza.Mu gusoza, ctDNA igira uruhare rwose mubibaho no guteza imbere HCC kandi irashobora gukoreshwa mugupima hakiri kare, gusuzuma kubaga, no gukurikirana indwara.
CTCs ni selile mbi ikomoka kubibyimba byambere cyangwa metastase metastasize kugeza mumaraso.Tumor selile isohora matrix metalloproteinase (MMPs), isenya igice cyo hasi, bigatuma selile yibibyimba yinjira mumaraso no mumitsi ya lymph.Nyamara, CTC nyinshi zirandurwa vuba na anoikis, igitero cyumubiri, cyangwa guhangayika.Inzibacyuho ya epiteliyale-mesenchymal (EMT) ituma CTC itandukana byoroshye nuduce twambere twibibyimba, gutera capillaries, no kubona ubuzima bwiza, metastasis, gutera, no kurwanya ibiyobyabwenge.Ubushakashatsi bwerekanye ko hariho itandukaniro rinini mu ngirabuzimafatizo zitandukanye mu bibyimba byibanze.Rero, isesengura rya CTC rirashobora kuganisha ku gusobanukirwa byimazeyo kubyimba selile itandukanye.54
Ibimenyetso byihariye kuri CTCs bifitanye isano na HCC harimo glypican-3 (GPC3), reseptor ya asialoglycoprotein (ASGPR), molekile ya epithelial selile adhesion (EpCAM) hamwe nibimenyetso bifitanye isano na selile nka CD44, CD90, 55 na molekile ya adhesion 1 (ICAM1).) .56 Ikimenyetso cya GPC3 ni selile membrane-ankore proteine ​​ikoreshwa mubuvuzi mu gusesengura indwara no kuranga HCC.57 Kugaragaza GPC3 bikunze kugaragara muri selile yibibyimba ya HCC hamwe no gutandukanya intera no hasi kandi bigatera kwimuka bidasanzwe;mubyongeyeho, kuba GPC3 + ​​CTCs byerekana HCC metastatike.58 ASGPR ni poroteyine ya transembrane igaragarira gusa hejuru ya hepatocytes kandi igaragara cyane muri HCC itandukanye cyane.EpCAM ni imwe mu zikoreshwa cyane muri poroteyine zifitanye isano no gufata CTCs.EpCAM yagaragaye nk'ikimenyetso cyo hejuru cy'utugingo ngengabuzima twa HCC dufite imiterere y'utugingo ngengabuzima, 59 ifitanye isano n'ibintu bitandukanye bivura indwara za HCC, nko gutera imitsi, gusuzuma urwego rwa AFP, ndetse na kanseri y'umwijima igeze ku bitaro bya Barcelona (BCLC).60 CTC EMT phenotype ni metastatike cyane.54 EMT inzira muri CTC iteza imbere metastasis ya HCC.Kugaragaza ibimenyetso bya EMT nka vimentin, twist, E-box zinc urutoki (ZEB) 1, ZEB2, snail, slug, na E-cadherin byakozwe muri CTC ikomoka ku mwijima ituruka ku barwayi ba HCC.58 Sisitemu ya CanPatrol yakozwe na Cheng [61] yashyize CTC mu matsinda atatu ya fenotipiki ashingiye ku bimenyetso byigaragaza cyane: epithelia phenotype (EpCAM, CK8 / 18/19), phenotype ya mesenchymal (vimentin, coiled), na fenotipike ivanze.Mu barwayi 176, CTC yose yarutaga AFP mu gutandukanya HCC n'indwara y'umwijima nziza.Indangagaciro za AUC kuri CTC zose, AFP, hamwe na CTC hamwe na AFP zose hamwe zari 0.774 (95% CI, 0.704–0.834), 0.669 (95% CI, 0.587–0.750), na 0.821 (95% CI, 0.756–0.886 ).).Ibyiciro bya CTC bishingiye kuri EMT birashobora guhanura indwara ya HCC, kugaruka hakiri kare, metastasis, nigihe gito muri rusange.
Kugeza ubu, uburyo bwo kumenya CSC burimo uburyo bwumubiri nuburyo bwibinyabuzima.Uburyo bufatika, bakunze kwita gutungisha bushingiye kumiterere ya biofiziki, ahanini biterwa nibintu bifatika bya CSC, nkubunini, ubucucike, kwishyuza, kugenda no guhindagurika.Ukurikije imiterere yumubiri, hariho uburyo butandukanye nka sisitemu ishingiye ku kuyungurura, dielectrophoresis, nibindi. Iyanyuma, izwi kandi nko gukungahaza immunoaffinity, ishingiye ahanini ku guhuza antigen-antibody kuva ubwo buryo bukoresha antibodies zirwanya biomarkers yihariye. nka EpCAM, ASGPR, reseptor 2 (HER2), ibyorezo byindwara ya epidermal yumuntu 2 (HER2), antigen yihariye ya prostate (PSA), pancytokeratin yumuntu (P-CK) na synthase ya karbamoyl fosifate 1 (CPS1).62 Ubundi bwoko, bwitwa uburyo bwo kudakungahaza, bukoresha cytometrike itemba kugirango itandukanye CTC na leukocytes ishingiye ku kigereranyo kinini cya kirimbuzi na cytoplasmeque nubunini.Kugeza ubu, ikizamini cyonyine cyemewe na FDA cyo kumenya CTCs ni Sisitemu-Gushakisha ™ sisitemu, ikoresha ibimenyetso bya selile ya EpCAM. Nyamara, ibimenyetso bifatika bishingiye kuri CTC gutahura bishobora kongera igipimo cyiza.54 Uruvange rwa antibodies zirwanya ASGPR na CPS1 rwageze ku gipimo cyo kumenya CTC ku kigero cya 91% mu barwayi ba HCC.63 Zhang n'abandi bakoresheje CTC-Chip hamwe na antibodies zirwanya ASGPR, P -CK na CPS1, kandi itandukanya abarwayi ba HCC n'abafite uburwayi bw'umwijima cyangwa kanseri itari HCC ku gipimo cya 100% .64 Ubushakashatsi bwakozwe na Wang bwagaragaje EpCAM + CTCs muri 60% by'abarwayi 42 ba HCC kandi bugaragaza isano iri hagati y’imyumvire yombi. igipimo n'umubare wa CTCs hamwe na TNM icyiciro.65 Guo n'abandi basanze amanota ya PCR yakomotse kuri PCR yazamutse mu barwayi 125/171 (73%) abarwayi ba AFP bari <20 ng / mL bafite sensibilité ya 72.5% na a umwihariko wa 95.0%, ugereranije na 57.0% na 90.0% kuri AFP muguhagarika 20 ng / mL.66 Ihuriro rya AFP na CTC rishobora kunoza imenyekanisha rya HCC.45 Bikekwa ko CTC ifite akarusho kuri AFP mugupima hakiri kare amatsinda ku kaga gakomeye kuri HCC. Nyamara, ibimenyetso bifatika bishingiye kuri CTC gutahura bishobora kongera igipimo cyiza.54 Uruvange rwa antibodies zirwanya ASGPR na CPS1 rwageze ku gipimo cyo kumenya CTC ku kigero cya 91% mu barwayi ba HCC.63 Zhang n'abandi bakoresheje CTC-Chip hamwe na antibodies zirwanya ASGPR, P -CK na CPS1, kandi itandukanya abarwayi ba HCC n'abafite uburwayi bw'umwijima cyangwa kanseri itari HCC ku gipimo cya 100% .64 Ubushakashatsi bwakozwe na Wang bwagaragaje EpCAM + CTCs muri 60% by'abarwayi 42 ba HCC kandi bugaragaza isano iri hagati y’imyumvire yombi. igipimo n'umubare wa CTCs hamwe na TNM icyiciro.65 Guo n'abandi basanze amanota ya PCR yakomotse kuri CTC yazamutse mu barwayi 125/171 (73%) abarwayi ba AFP bari <20 ng / mL bafite sensibilité ya 72.5% na a umwihariko wa 95.0%, ugereranije na 57.0% na 90.0% kuri AFP muguhagarika 20 ng / mL.66 Ihuriro rya AFP na CTC rishobora kunoza imenyekanisha rya HCC.45 Bikekwa ko CTC ifite akarusho kuri AFP mugupima hakiri kare amatsinda ku kaga gakomeye kuri HCC.Nyamara, ibimenyetso bifatika hamwe no kumenya CTCs bishobora kongera ijanisha ryibisubizo byiza.54 Uruvange rwa antibodiyide zirwanya ASGPR na CPS1 rwageze ku gipimo cya CTC cya 91% ku barwayi bafite HCC.63 Zhang n'abandi.yakoresheje CTC-Chip ifite antibodies zirwanya ASGPR, P-CK na CPS1, kandi inatandukanya abarwayi barwaye HCC n'abafite uburwayi bwumwijima cyangwa abatari HCC ku gipimo cya 100%.частота и количество ЦОК содидией TNM.65 Guo и соавторы обнаружили, что показатель ПЦР, полученный из ЦОК, был повшенен у 125/171 (73%) адов, у котинх охововь АФП был <20 нг / с с сп групп. inshuro n'umubare wa CTCs hamwe na TNM icyiciro.65 Guo nabandi basanze PCR yakomotse kuri CTC yazamuwe mubarwayi 125/171 (73%) bafite urwego rwa AFP <20 ng / mL bafite sensibilité ya 72.5% kandi umwihariko wa 95.0% ugereranije na 57.0% na 90.0% kuri AFP kurwego rwo guca kuri 20 ng / mL.66 Ihuriro rya AFP na CTC rishobora kunoza itahurwa rya HCC.45 CTC zifatwa nkizifite inyungu kuri AFP mugupima hakiri kare amatsinda.hamwe ningaruka nyinshi za HCC.Ariko, marikeri ishingiye hamwe gutahura CTCs irashobora kongera ijanisha ryibisubizo byiza.54 Uruvange rwa antibodiyide zirwanya ASGPR na CPS1 zageze ku gipimo cya 91% CTC ku barwayi bafite HCC.63 Zhang n'abandi.yakoresheje chip ya CTC hamwe na antibodies zirwanya ASGPR, P-CK na CPS1 kandi itandukanya abarwayi barwaye HCC n'indwara y'umwijima nziza kandi itari HCC hamwe 100%.64 Ubushakashatsi bwa Wang bwerekanye 60% bya EpCAM + CTCs ku barwayi 42 ba HCC kandi bwerekanye isano iri hagati y’indwara n’umubare wa CTC ku cyiciro cya TNM. 65 Guo 等 人 发现 ， 在 AFP 水平 <20 ng / mL 的 125/171 (73%) 名 患者 中 TC CTC 衍生 的 PCR 评分 升高 ， 敏感性 为 72.5% ， 特异性 为 95.0% ， 而 AFP 在 截止值为 20 ng / mL 时 的 特异性 为 57.0% 和 90.0%。 65 Guo 等 人 发现 在 在 在 水平 <20 ng / ml 的 125/171 (73%) 名 患者 ， ， ctc 衍生 pcr 评分 ， 敏感性 为 为 72.5% ， 5. 95.0% ， AFP 在 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 ng ng ng ng ng ng 20ng / mL 时 的 特异性 为 57.0% 和 90.0%。65 Guo n'abandi.обнаружили, что у 125/171 (73%) отсечки Специфичность соверляла 20 нг / бар. yasanze ko muri 125/171 (73%) abarwayi bafite urwego rwa AFP <20 ng / mL, indangagaciro za PCR zikomoka kuri CTC zazamuwe hamwe na sensibilité ya 72.5% kandi umwihariko wa 95.0%, mugihe AFP yari yihariye. yari 20 ng / mL.ml yari 57.0% na 90.0%.66 Guhuza ORP na CTC biteza imbere kumenya HCC.45 CTC zitekereza ko zisumba AFP mugusuzuma hakiri kare abaturage bafite ibyago byinshi bya HCC.Rero, kuri CTC-nziza kandi ifite ibyago byinshi byamatsinda ya HCC, ibizamini bya CTC bigomba guhuzwa buri gihe na ultrasound na AFP.Nyamara, CTC ifatwa nkibintu byingenzi byerekana ibibyimba metastasis no kugaruka, kandi kumenya CTC ntabwo byemewe kubwigikoresho cyo gusuzuma.62 Kubwibyo, CTC irashobora gukora nka biomarker nziza yo guhanura kuruta ibindi bimenyetso bikoreshwa ubu. Zhou n'abandi basanze abarwayi bafite umubare munini wa EpCAM + CTCs na selile T bagenzura bagaragaje ibyago byinshi byo kwandura HCC, kurusha abafite umubare muto wa CTCs, hamwe na 66.7% vs 10.3% (P <0.001) .67 Ubushakashatsi nk'ubwo bwatangajwe na Zhong et al.68 Byongeye kandi, Qi yasanze abarwayi 101 kuri 112 (90.81%) barwaye HCC, harimo n'abafite uburwayi bwo mu cyiciro cya mbere, banduye CTC kandi ko hamenyekanye udusimba duto cyane twa HCC nyuma ya 3 kugeza ku mezi 5 yo gukurikirana. Zhou n'abandi basanze abarwayi bafite umubare munini wa EpCAM + CTCs hamwe n’utugingo ngengabuzima T bagaragaje ibyago byinshi byo kwandura HCC kurusha abafite umubare muto wa CTCs, hamwe na 66.7% vs 10.3% (P <0.001) .67 A ubushakashatsi nk'ubwo bwatangajwe na Zhong et al.68 Byongeye kandi, Qi yasanze abarwayi 101 kuri 112 (90.81%) barwaye HCC, harimo n'abafite uburwayi bwo mu cyiciro cya mbere, banduye CTC kandi ko hamenyekanye uduce duto cyane twa HCC nyuma ya 3 kugeza Amezi 5 yo gukurikirana. Чжоу и др.обнаружили, что у уанов с повышенным количеством ЦОК EpCAM + и уторторных Т-клеток риск развития рецидива ГЦК был вше, чем у уков с низким количеством ЦОК, с коэпатовентом рецидивов. Zhou n'abandi basanze abarwayi bafite EpCAM + CTCs hamwe na selile T igenzura bafite ibyago byinshi byo kongera kugaruka kwa HCC kurusha abafite CTC nkeya, aho byagarutsweho na 66.7% vs 10.3% (P <0.001) 67.Ubushakashatsi nk'ubwo bwakozwe na Zhong n'abandi.6. Zhou 等 人 发现 ， 与 CTC 数量 较少 的 患者 相比 ， EpCAM + CTC 和 调节 性 T 细胞 数量 升高 的 发生 HCC 复发 的 风险 更高 ， 复发 率 分别 6. 66.7% 和 10.3% (P <0.001)。 Zhou 等 人 发现 与 ctc 数量 少 的 患者 相比 ， epcam + ctc 和 t 细胞 数量 的 cc hcc 复发 风险 更 cc cc 率 为 为 3 3 3 3 3 3 3 p <0.001) 。。。。。。。。。。。。。。。 Чжоу и др.обнаружили, что у кв с с повышенным количеством ЦОК EpCAM + и угторторных Т-клеток имели более всокий риск рецидива ГЦК по сравнению с сенентами с меньшим количеством ЦОК, с ччовогы. Zhou n'abandi.yasanze abarwayi bafite EpCAM + CTCs hamwe na selile T igenga bafite ibyago byinshi byo kongera kugaruka kwa HCC ugereranije n’abarwayi bafite CTC nkeya, aho usanga 66.7% na 10.3% (P <0.001).Ubushakashatsi nk'ubwo bwatanzwe na Zhong n'abandi.68 Byongeye kandi, Qi yasanze 101 ku barwayi 112 ba HCC (90.81%), harimo n’abarwayi barwaye hakiri kare, bagize ibisubizo byiza bya CTC kandi basanga udusimba duto cyane twa HCC nyuma yo gusurwa 3.Indorerezi kugeza ku mezi 5.Basanze kandi CTCs ku barwayi 12 barwaye HBV idakira kandi basanga ibibyimba bito bya HCC bitarenze amezi 5 ku barwayi 2 ba CTC.69 Rero, CTCs irashobora gukoreshwa muguhishurira HCC, 70 ariko irashobora gukoreshwa muburyo busanzwe nkibinyabuzima byerekana.
Kimwe na cfDNA, cfRNA irekurwa mumaraso binyuze muri sisitemu zitandukanye.Izi molekile ziri mumaraso ya peripheri zerekana kanseri ya kanseri ikomoka.Ugereranije na marikeri zagaragajwe nuburyo budatera, cfRNAs ziragenzurwa cyane, zihariye, kandi nyinshi mubidukikije bidasanzwe.Ubusobanuro n'agaciro ko gusuzuma 71 miRNAs (miRNAs) muri HCC byavuzwe mubushakashatsi bwinshi.miRNAs ni endogenous non-code RNAs (ncRNAs) igenga ibikorwa bitandukanye bya biologiya biologiya ihagarika ibisobanuro byintumwa za RNAs (mRNAs).miRNAs iri mumibiri ya apoptotique ikubiye muri exosomes, ariko irashobora kandi guhuza neza na proteyine za serumu na lipide mumaraso ya peripheri kandi birashobora gukoreshwa mugusuzuma HCC.microRNAs igira uruhare mu kuvugurura umwijima, metabolism ya lipide, apoptose, gutwika, no guteza imbere HCC.72 Oncogenic miRNAs nka miR-21, miR-155 na miR-221 birazwi cyane muri HCC.By'umwihariko, miR-21 igira uruhare runini muri synthesis ya kolagen muri matrice idasanzwe na fibrosis kandi igatera hepatocarcinogenezi ikora ingirabuzimafatizo ya hematopoietic.72,73 suppressor ya Tumor miRNAs muri HCC harimo miRNA-122, miRNA-29, umuryango wa Let-7, n'umuryango wa miRNA-15.Umuryango Let-7 ugizwe na suppressor yibibyimba byinshi miRNA yibasira umuryango wa RAS.Umuryango wa miR-15 urimo miR-15a, miR-15b, miR-16, miR-195, na miR-497, bifite gahunda zuzuzanya kuri mRNA zimwe.Byongeye kandi, RNAs ndende idafite kodegisi (lncRNAs) hamwe na RNAs izenguruka (cirRNAs) nabyo ni ngombwa mugusuzuma hakiri kare HCC.lncRNAs igereranya icyiciro kinini cya ncRNAs, harimo na mRNA isa na ncRNAs, kandi igira uruhare mubitera indwara nyinshi zabantu.LncRNAs igira uruhare mukugenzura umwijima microen ibidukikije n'indwara zumwijima zidakira.74 CircRNAs nayo nicyiciro cya ncRNAs ifite imirimo myinshi mugutunganya imvugo ya gene.Vuba aha, circRNAs yafashwe nkibikoresho byo gusuzuma HCC.
Kuzenguruka kwa RNA kubuntu bifite ituze ridasanzwe, harimo kurwanya ubushyuhe, pH, na RNase, bigatuma kwigunga kwa fnRNA kumaraso ya peripheri bitarambirana hakoreshejwe uburyo busanzwe bwo kweza RNA.Uburyo bukoreshwa cyane harimo NGS, microarray na RT-qPCR.NGS yemerera microRNAs gupimwa muri genome yose.Nyamara, ubu buryo buhenze kandi isesengura ntabwo risanzwe.Ibinyuranye, RT-qPCR ntabwo ihendutse, yongerera vuba aside nucleique, kandi itanga ibyiza byinshi nko kumva neza, kumenya neza, kwaguka kwinshi, no gusaba ingero nke.Microarrays nubundi buryo bukoreshwa mugutahura miRNA hashingiwe ku buryo bworoshye kandi bwihariye bwo guhuza intego ya miRNAs hamwe na ADN zuzuzanya, 75 ariko gusesengura amakuru ya microarray biratwara igihe.
Kuzenguruka miR-122 na Let-7 byavuzwe ko bishobora kuba ingirakamaro mu gusuzuma HCC yo hambere mu matsinda y’ibyago byinshi, ibimenyetso ku barwayi bafite indwara ya HBV ifitanye isano na nodules na HCC yo hambere.76 Cai n'abandi.basanze abagize umuryango wa Let-7 (miR-92, miR-122, miR-125b, miR-143, miR-192, miR-16, miR-126, na miR-199a / b) bafite ibyago byo karande HCC mu barwayi barwaye hepatite.Umuryango wa Let-7 urashobora gukora nka biomarker ya surrogate nziza yo guhanura iterambere rya HCC mumatsinda afite ibyago byinshi bifitanye isano na hepatite idakira C. 77 miR-122 ifite ubuziranenge bwo kwisuzumisha mugutahura HCC hakiri kare kubarwayi barwaye cirrhose.Serumu ikwirakwiza MiR-107 nayo yasuzumwe mugihe cyambere cya HCC, 79 kandi yerekanye ubushobozi bwiza mubantu bafite ibyago byinshi.Zhou et al yatangaje ko itsinda rya miRNAs (miR-122, miR-192, miR-21, miR-223, miR-26a, miR-27a na miR-801) rishobora gutandukanya HCC na hepatite idakira B (CHB) na cirrhose ibyiyumvo byari 79.1% na 75%, kandi byihariye 76.4% na 91.1%.80 Muri HCC ifitanye isano na HBV, twasanze urwego rwa miR150 rwaragabanutse cyane ugereranije n’abarwayi ba HBV badakira badafite HCC (sensibilité 79.1%, umwihariko 76.5%).-224 yazamuwe muri HCC ugereranije no kugenzura neza, kandi isesengura ryitsinda ryerekanye urwego rwo hejuru kubarwayi bafite HCC bafitanye isano na HBV.hepatite B ifitanye isano na cirrhose hamwe n’abarwayi ba HCC bagaragaje ibyiciro bya siRNA birimo siRNA zirindwi zitandukanye zitandukanye zishobora kumenya HCC muburyo butandukanye;Urutonde rwa AUC mugupima hakiri kare kurenza abakorerabushake ba AFP.Basanze miRNA enye (miR-1972, miR-193a-5p, miR-214-3p, na miR-365a-3p) zishobora gutandukanya abarwayi bafite HCC n’abarwayi badafite HCC.MiRNA eshanu zikabije (miR-122-5p, miR-125b-5p, miR-885-5p, miR-100-5p, na miR-148a-3p) zifatwa nk'indwara zishobora kwandura HBV muri HCC, cirrhose, na biomarkers ya CHB, cyane cyane miR-34a-5p irashobora kuba biomarkers yumwijima cirrhose, 85 kandi irashobora kuba biomarkers yo gusuzuma hakiri kare HCC mubantu bafite ibyago byinshi.LncRNA yize cyane muri HCC ikora cyane muri kanseri yumwijima (HULC).Ubundi bushakashatsi bwerekanye ko HULC izenguruka mu barwayi ba HCC ishobora gukoreshwa nk'ikimenyetso cyo gusuzuma kuko iyi lncRNA itunganijwe cyane mu barwayi ba HCC ugereranije n'abantu bafite ubuzima bwiza.71,86 Mubindi lnRNAs, LINC00152 ifatwa nkurutonde rwiza rwo gusuzuma lncRNA kubera AUC yo hejuru, ibyiyumvo byihariye kandi byihariye.86 Mu bushakashatsi bumwe, imvugo y’amaraso ya LINC00152 yagiye yiyongera buhoro buhoro kuva ku buzima busanzwe ku barwayi barwaye CHB na cirrhose, kandi amaherezo yari hejuru muri HCC.Ubushakashatsi bwakozwe ku mvugo ya circSMARCA5 muri plasma y’abarwayi bafite HCC bwerekanye ko igabanuka ry’imvugo muri HCC kuva kuri hepatite kugeza kuri cirrhose ndetse no gukomeretsa mbere.87 Isesengura ry’imirongo ya ROC ryemeje ubushobozi bwiyi circRNAs mu gutandukanya abarwayi bafite hepatite cyangwa cirrhose yumwijima nabafite HCC, cyane cyane abafite urwego rwa AFP munsi ya 200 ng / mL.Byongeye kandi, Zhu yasesenguye RNAs 13,617 ziri mu cyitegererezo cya plasma cy’abarwayi ba HCC bafitanye isano na HBV yemeza ko RNAs 6 y’amagare yagaragaye mu buryo butandukanye muri cirrhose ya HCC na HBV, byerekana ko cRNAs zishobora kuba ingirakamaro.ibimenyetso byo gusuzuma hakiri kare amatsinda afite ibyago byinshi nkibifitanye isano n'indwara y'umwijima, abarwayi ba sclerose.88
Exosomes ni membrane viticles 40-160 nm ya diameter;imitsi myinshi yo mu nda ihuza hamwe na selile ya selile hanyuma ikarekurwa muri matrise idasanzwe.Harimo ibintu byinshi bikora, birimo lipide, proteyine, RNA na ADN, kandi bigira uruhare runini mu itumanaho hagati ya selile, HCC na selile zitari HCC.89,90 Exosomes igenga iterambere rya HCC ikora fibroblast ya hepatocyte na selile stellate, selile immunite, hepatocytes isanzwe, na selile HCC.91 Muri microen ibidukikije yibibyimba, selile yibibyimba itanga umubare munini wa exosomes ikurwa mumasemburo ya kanseri ikajya mu ngirabuzimafatizo zidakuze, nazo zikagira uruhare muri oncogenezi, kwangirika, no kwerekana ibimenyetso bya selile.92 Ubushakashatsi bwerekanye ko exosomes ishobora kwimurira oncogène mu ngirabuzimafatizo zisanzwe mu gihe cy’indwara ya pologologi, ishobora kuba imwe mu nzira zo gutera ibibyimba na metastasis.93 Uruhare rwa exosomes mugutera kanseri irashobora kuba imbaraga kandi yihariye ubwoko bwa kanseri, 89 Exosomes irashobora kwinjizwa mumasoko yegeranye cyangwa ya kure kugirango igenzure ingirabuzimafatizo zitandukanye mu ngirabuzimafatizo zakira zishobora kugira uruhare mu itumanaho ry’imikorere hagati y’imikoranire n’imikoranire ya mikorobe y’ibidukikije, barashobora guhuza ibimenyetso bya selile na metabolism.94 Ibiranga nimpinduka zingirakamaro za molekile yimizigo ya exosome yerekana mu buryo butaziguye ibiranga nimpinduka zingirakamaro zingirabuzimafatizo yibibyimba byababyeyi, 95 ari nayo shingiro ryo gukoresha exosomes mugupima no gutangaza kanseri, ndetse no guhanura buri muntu ku giti cye ku buvuzi bwa antikanseri. ..96
Uburyo bwa laboratoire gakondo yo gutandukanya no gusesengura exosomes biragoye, intambwe nyinshi, kandi bitwara igihe, harimo ultracentrifugation, kuyungurura, gukuramo ingano ya chromatografiya, kweza immunoaffinity, guhanagura iburengerazuba, enzyme ihuza immunosorbent assay (ELISA), PCR, hamwe nisesengura ryamazi.sisitemu ntoya hamwe na laboratoire kuri chip ikoresha mikoro / nanotehnologiya irimo gutezwa imbere byihuse, byoroshye muburyo bwo kwigunga kwa exosomes.Isesengura rya Nanoparticle (NTA) nuburyo bukoreshwa cyane mu kuranga ingano nubunini bwa exosomes, harimo nuburyo nka magnetiki nanoparticles na polyhydroxyalkanoates.Uburyo bwa Microfluidic na electrochemique burashobora kandi gutahura vuba exosomes kumusaruro mwinshi.
Poroteyine za Exosomal ni ibimenyetso byingenzi byo gusuzuma HCC.Mu bushakashatsi bwa Arbelaiz, urwego rwa 98 RasGAP SH3 ruhuza poroteyine (G3BP) na reseptor ya immunoglobuline ya polymeric (PIGR) rwazamutse cyane muri exosomes ikomoka kuri HCC, kandi gushyira hamwe kwa poroteyine zombi byari byiza kuruta ibya AFP.Kurenza ibyuma ni ikintu cyingenzi kigira uruhare mu iterambere rya HCC.Tseng yatangaje ko hepcidine ishobora kugira uruhare runini mu kurwanya HCC.99 Exosomes ikomoka kuri sera y'abarwayi ba HCC yari ifite umubare munini cyane wa kopi ya hepcidine mRNA itandukanye na bagenzi babo bafite ubuzima bwiza, byerekana ko hepcidine ishobora kuba igitabo gishya cyo gusuzuma indwara ya HCC.Poroteyine 14-3-3ζ muri exosomes ikorwa na 100 HCC irashobora kugabanya imikorere ya T selile, gukwirakwizwa, no gutandukana kandi irashobora gutuma selile ihinduka T selile igenga T, bigatuma T selile igabanuka.101 Ibi bishyigikirwa nubushakashatsi bwinshi bwakoze iperereza ku kwirinda ibibyimba bivuye ku gukingira indwara, 102 bishobora kugira uruhare muri HCC tumorigenez.
Usibye kuba ecRNA iba muri plasma cyangwa serumu, exosomes ikungahaye kuri RNA irashobora gukoreshwa mugihe cyo kudatera igihe mugihe cyo gusuzuma ibibyimba hakiri kare no kumenya ubwihindurize bwibibyimba hamwe nuburyo bwo kuvura.Urwego rwa exosomal miRNA-21 muri serumu yamaraso mu itsinda rya HCC rwikubye inshuro 2,21 ugereranije n’itsinda rya CHB, naho mu itsinda rya HCC ryikubye inshuro 5.57 ugereranije n’abaturage bafite ubuzima bwiza.Mu bushakashatsi bwa Wang, exosomes yiyongereye cyane HCC ugereranije n’abarwayi ba cirrotique bafite agaciro ka 0.83 (95% CI 0,74–0.93) na 0.94 (95% CI 0.88–1.00).104 Amakuru yabonetse yasobanuye uruhare rwa molekile yimizigo idasanzwe ya exosomal mugutunganya oncogenezi niterambere rya HCC.105 Imvugo ya serumu ya miR-221, miR-103, miR-181c, miR-181a, miR-93 na miR-26a irahuye.na metastasis, na miR21 urwego rwarushijeho kuba rwinshi kubarwayi ba HCC kuruta kugenzura neza ndetse no ku barwayi ba CHB.102 LncRNA yari ifite agaciro ko kwisuzumisha muri HCC.Ubushakashatsi bwerekanye ko exosomes ikomoka kuri sera yabarwayi ba HCC ifite urwego rwo hejuru cyane rwa LINC00161, LINC000635, na lncRNA ikora muguhindura ibintu bikura-β kuruta kubarwayi badafite HCC, kandi lncRNAs zifitanye isano cyane nicyiciro cya TNM nubunini bwibibyimba.110 Conigliaro n'abandi.CD90 + exosomes yasanze igaragaza urugero rwinshi rwa lncRNAH19, yongereye cyane ibintu bikura byimitsi iva mu mitsi (VEGF) no gusohora reseptor ya VEGF-R1, bityo bitera angiogenez.93 CircRNAs nubundi bwoko bwa exosomal ncRNAs - igaragazwa kurwego rwo hasi ariko ruhamye kurwego rwibinyabuzima, circRNAs nayo yerekana umwihariko wubwoko bwakagari, ubwoko bwimyenda, icyiciro cyiterambere, nibikorwa byubuyobozi.111 circRNAs ni biomarkers isuzuma kanseri hakiri kare kandi ntoya.112 Ibizamini bya kliniki biherutse kwerekana ko umwihariko wa miRNAs mu guhanura HCC atari byiza.Kubwibyo, gutahura bigoye ukoresheje ubushakashatsi bwinshi (urugero, miR-122 na miR-48a bifatanije na AFP) birashobora kunoza imenyekanisha rya HCC hakiri kare no gutandukanya HCC na cirrhose.100
Abarwayi bafite CHB na cirrhose yumwijima nitsinda rikunze kwibasirwa cyane na HCC.Ku matsinda afite ibyago byinshi, iyo igisubizo cya virusi gikomeje kugerwaho, ingamba zo kugenzura zihenze zishingiye ku ngaruka za HCC zigomba gutegurwa, kandi gusuzuma hakiri kare ni urufunguzo rwo kunoza isuzuma no kuvura HCC hamwe n’igiciro kinini cyo gukoresha neza2 ..Uburyo bwo gusuzuma hakiri kare kanseri bufite aho bugarukira: uburyo bwiza bwo gusuzuma hakiri kare ntabwo bwashyizweho kubwoko bwa kanseri, kandi kubahiriza ni bike.Ugereranije nuburyo gakondo bwo kwisuzumisha hakiri kare, tekinoroji ya biopsy yamazi ifite ibyiza bigaragara: koroshya icyitegererezo, gutahura panrac, uburyo bwiza bwo kubyara, hamwe nigisubizo cyiza kubibyimba bitavutse.Urebye ikiguzi-cyiza cyuburyo bujyanye na biopsy yamazi, imikoreshereze yabyo mugusuzuma HCC ntabwo yigeze igeragezwa.Nubwo hari iterambere ryagaragaye neza kurwego rwa molekile, biopsy yamazi ihenze kumenya HCC kubarwayi bagenewe, bikagabanya imikoreshereze yayo myinshi ugereranije nuburyo bwihariye bwo gufata amashusho nka ultrasound na magnetic resonance imaging.113.114 Nyamara, ubushakashatsi bwibanze bwerekanye ko biopsy yamazi yerekanaga inyungu zikomeye mubijyanye nubuzima bwahinduwe neza (QALYs).115 Ibyiza bya biopsy yamazi muri kanseri yambere yigifu na nasofarynx nabyo byagaragaye.116,117 Ibiriho ubu ni uko biopsy yamazi ishobora kuzuza serumu biomarkers no gusuzuma radiologiya mugutahura no gusuzuma ibibyimba.117 118
Dukurikije ubuvanganzo bwa none, tekinoroji ya biopsy yerekanaga cyane cyane ibyiyumvo byihariye kandi byihariye mugupima hakiri kare amatsinda ashobora kwandura kanseri y'umwijima.Hatitawe ku bwoko bwa biopsy y'amazi, irashobora gutandukanya HCC n'abantu bafite ibyago byinshi badafite HCC, byerekana akamaro ko kwisuzumisha hakiri kare kuko itandukaniro riri hagati y’ibyago byinshi n’abantu bafite ubuzima bwiza rigaragara.ctDNA ifite ubuzima bucye bwigihe gito kandi irashobora gukoreshwa mugutahura HCC, kubwibyo rero impinduka zose zatewe na cDNA zikomoka kumibyimba zirashobora gutanga ibimenyetso bifatika byerekana ibimenyetso bifatika byerekana iterambere ryibibyimba, cyane cyane kubyimba bito.Urwego rwo hejuru rwa ctDNA rwerekana iterambere no gukwirakwiza kanseri kandi ni ikimenyetso cyambere cyo gutera imbere no kugaruka.Byongeye kandi, ukurikije ibisubizo bya ctDNA, abarwayi barashobora kwivuza kugiti cyabo no kubakurikirana.119 Imbuga zihariye za methylation zishobora kuba ikimenyetso cyiza kuruta AFP kugirango tumenye hakiri kare HCC na cirrhotic nodules.Mubibazo bidasubirwaho bya HCC, urwego rwinshi rwa cDNA rwerekana kwibasirwa na mikorobe-mitsi hamwe no kongera kwibaruka na metastasis.Guhindura nimero ya kopi bifitanye isano no kubaho kw'abarwayi bafite HCC.Turashobora kwiyumvisha ko isuzuma rya cDNA rishobora kugira uruhare mubuvuzi rusange bwa HCC, kandi cDNA irashobora kuba ikimenyetso cyerekana uburyo bwo kuvura.Ibimenyetso bishingiye ku ihinduka ry’imiterere yihariye ya ctDNA byemejwe n’amabwiriza y’ubuvuzi kugira ngo hamenyekane ingaruka no kugenzura ibiyobyabwenge.kwipimisha ctDNA birashobora kuba ibikoresho byingirakamaro byamazi ya biopsy yo gusuzuma hakiri kare.CTC nayo igira uruhare runini mugusuzuma hakiri kare amatsinda ya HCC afite ibyago byinshi.Ibimenyetso bitandukanye bya HTC bifitanye isano na CTC bifite akamaro kanini mugutangira, iterambere, no kugaruka kwa HCC.Nka membrane viticles, exosomes igira uruhare mu itumanaho hagati, cyane cyane muri selile HCC.Kuzenguruka microRNAs ihamye mumaraso bityo birashobora kuba ingirakamaro mugupima hakiri kare HCC.Buhoro buhoro, poroteyine za exosomal na Exosomes zikungahaye kuri RNA byavumbuwe, kandi ingaruka zazo zo guhanura HCC zemejwe.Igishimishije, etiologiya zitandukanye za HCC zishobora nanone guhuzwa na mutation zitandukanye, bityo dushobora guhitamo biomarkers zitandukanye kugirango dusuzume hakiri kare dushingiye kuri etiologiya zitandukanye za HCC.120
Nyamara, tekinoroji ya biopsy yubu irakemangwa mubijyanye no gutuza kandi ntishobora kwigenga kwipimisha hakiri kare cyangwa kugenzura HCC, ariko irashobora kuzuzanya kwisuzumisha no kwisuzumisha.121 Nuburyo bwa biopsy yamazi, gutahura no gufata amashusho ya ctDNA, CTC, cfRNA hamwe na AFP cyangwa PIVKA-II bifitanye isano na exosome bifite ibyifuzo byokwisuzumisha hakiri kare no gutangaza HCC.Nyamara, uburyo nyabwo bwo kurekura ctDNA mumaraso buracyasobanurwa.Kugaragaza ibinyabuzima shingiro bya ctDNA birashobora koroshya imikoreshereze yikimenyetso.Umubare muto wa ctDNA mukuzenguruka hamwe nibisabwa bikenewe byo gukemura ibibazo ni imbogamizi zo gushyira mubikorwa ivuriro rya cDNA muri HCC.Byongeye kandi, ihinduka ry’irondakoko ntirifite ibintu byihariye byemerera kumenya neza kanseri.Kubera ko ubwoko bwinshi bwa genetike na somatike nabwo bugaragara mubice bisanzwe, ihinduka ryimiterere ryerekanwe na fluid biopsy rishobora kuba ingirakamaro mugupima hakiri kare HCC.122 Imipaka yintego zisobanutse neza zingirakamaro hamwe na biomarkers zifasha gutandukanya cDNA na ADN itari ibibyimba nibibazo byingenzi mugukoresha cDNA.kubura akamaro k'ibimenyetso byoroshye kandi byihariye byo kumenya CTCs.Gusa selile zifatika zifite ubushobozi bwa metastatike zabonetse, kandi guhuza neza ibimenyetso bya CSC bikungahaye ntibyari bisobanutse.Gutandukanya CTCs kumuco no gusuzuma imyirondoro yabo nayo ni umurimo utoroshye.Bitewe nibibazo bijyanye no kumenya, kwigunga no kweza exosomes, uburyo bwihariye bwa molekile buracyasobanutse, kandi ubushakashatsi bwibanze ku buryo bwa exosomes na HCC ntabwo bwimbitse, kandi uburyo miRNAs, lncRNAs, na proteyine byashyizwe muri exosomes. , kandi ntibisobanutse niba gufata exosome ari inzira yihariye.Gukoresha exosomes mugupima no kuvura HCC biracyari mubyiciro.Kutagira ubuziranenge bwibikorwa bya biopsy byamazi, nkubwoko bwigituba gikoreshwa mugukusanya amaraso, ubwinshi bwamaraso, kubika icyitegererezo no gutahura, kwigunga no gukungahaza, birashobora kubuza kubikoresha mubikorwa byubuvuzi bisanzwe kubera itandukaniro mubikorwa bitandukanye mubigo nderabuzima.Ingaruka za biopsy yamazi mugupima hakiri kare, gusuzuma, gusuzuma neza, no guhanura HCC iracyashakishwa, cyane cyane kumatsinda afite ibyago byinshi.Ikoranabuhanga rya biopsy rifite ubushobozi bukomeye kandi biteganijwe ko rizakoreshwa cyane mubikorwa byubuvuzi bwa kanseri yumwijima mugihe cya vuba.
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Igihe cyo kohereza: Nzeri-23-2022