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Ding Jingnuo, Zhao Weifeng, Ngalaba Ọrịa na-efe efe, Ụlọ Ọgwụ Njikọ Mbụ nke Mahadum Suzhou, Suzhou City, Jiangsu Province, 215000 Tel.etuto ahụ nke sistemu digestive nwere ndụ n'ozuzu afọ 5 nke 14.1%.A na-achọpụta ọtụtụ ndị ọrịa nwere HCC n'ọkwa dị elu, yabụ nyocha mbụ dị mkpa iji belata ọnwụ site na HCC.Na mgbakwunye na ihe ngosi nchọpụta a na-ejikarị eme ihe dị ka serum alpha-fetoprotein (AFP), lectin-reactive alpha-fetoprotein (AFP-L3), na prothrombin na-adịghị mma (protein K erughi protein II, PIVKA-II), usoro biopsy mmiri. E gosiputara na ọ bara uru nchoputa na nchọpụta nke HCC.E jiri ya tụnyere usoro mkpasu iwe, biopsy mmiri nwere ike ịchọpụta metabolites ọjọọ na-ekesa.Usoro mmiri mmiri mmiri na-achọpụta mkpụrụ ndụ tumor na-ekesa, DNA tumor na-ekesa, na-ekesa RNA, na exosomes ma na-eji ya maka nyocha mmalite, nchọpụta, na nyocha prognostic nke HCC.Edemede a na-enyocha usoro ihe omimi ihe omimi na itinye usoro biopsy dị iche iche iji kewapụ ndị na-ekwe nkwa biomarkers nke nwere ike ịbụ nhọrọ dị mma maka ntule mbụ nke HCC iji kwalite nyocha mmalite nke otu HCC nwere nnukwu ihe egwu.Keywords: Usoro biopsy nke mmiri, hepatocellular carcinoma, otu ihe egwu dị elu.
Hepatocellular carcinoma (HCC) bụ akpụ akpụ akpụ akpụ nke tract digestive, n'ọkwa nke isii n'ime ọrịa ọhụrụ nke etuto ọjọọ na ma nwoke ma nwanyị.1 Gburugburu ụwa, ọrịa kansa imeju bụ ihe nke atọ na-ebute ọnwụ kansa mgbe akpa ume na ọrịa cancer agba na-akpata, na-akpata 8.3% nke ọnwụ metụtara ọrịa kansa site na neoplasms ọjọọ niile.1 Amụma nke HCC nwere njikọ chiri anya na ọkwa na nchoputa.Isi ihe kpatara ndụ na-adịghị mma na HCC bụ metastases intrahepatic, portal venous tumor thrombi, na metastases dị anya na-egbochi ịghaghachi, na ọtụtụ n'ime njirimara ndị a adịlarị na ndị ọrịa n'oge nyocha.
Dabere na nchọpụta nchọpụta na ntuziaka ọgwụgwọ, isi ihe ize ndụ maka ịmepụta HCC bụ cirrhosis nke imeju, ọrịa ịba ọcha n'anya B (HBV) ma ọ bụ nje ịba ọcha n'anya C (HCV), ọrịa imeju na-egbu egbu, na ọrịa imeju na-adịghị egbu egbu (NAFLD). ).2 Tụkwasị na nke ahụ, ihe ndị dị ize ndụ maka HCC gụnyere oriri aflatoxin-emetọọ, schistosomiasis, ihe ndị ọzọ na-akpata cirrhosis, akụkọ ihe mere eme ezinụlọ nke ọrịa cancer imeju, ọrịa shuga, oke ibu, ise siga, na mmerụ ahụ nke ọgwụ na-akpata.Otu dị afọ 35 na 45 nwere nnukwu ihe ize ndụ kwesịrị ịdị na-enyocha ahụike mgbe niile.Nyocha mbụ bụ usoro ọgwụgwọ mmalite dị mkpa iji meziwanye ndụ zuru oke nke ndị ọrịa nwere HCC.
A na-akwado ndị na-ahụ maka biomarkers dị ka AFP, AFP-L3 na PIVKA-II maka nyocha mbụ nke HCC3,4.Usoro biopsy nke mmiri mmiri egosila nsonaazụ dị mma na nyocha mmalite na nyocha ọgwụgwọ.5,6 Enweela ọganihu dị ịrịba ama na HCC mmiri mmiri biopsy, nke nwere ike inwe mmetụta dị elu na nkọwa karịa akara akara serum dị ka AFP (Table 1).
AFP bụ ihe na-ahụ maka biomarker nke a na-ejikarị na HCC ma ugbu a bụ biomarker kachasị zuru oke nke a na-ejikarị maka nyocha mmalite, nyocha na nyocha nke ọrịa ahụ.A na-ewere ọkwa AFP dị elu na-adịgide adịgide dị ka ihe ize ndụ maka ọganihu nke HCC.7,8 Ọnụ ọgụgụ nchọpụta nke obere hepatocellular carcinoma (sHCC) na-amụba site na mmepe nke ultrasound na computed tomography, na AFP achọpụtala na ọ naghị emetụ n'ahụ na nchọpụta nke hHCC na omume ụlọ ọgwụ.Dika ntughari otutu ihe omumu9, achoputara ihe oma AFP na 46% (616/1338) nke ikpe HCC na 23.4% (150/641) nke ikpe sHCC.Na mgbakwunye, ọkwa AFP na-ebuli elu na ndị ọrịa nwere ọrịa imeju na-adịghị ala ala na cirrhosis.10 Ya mere, AFP nwere oke nyocha nyocha maka sHCC.11 Dị ka Asia-Pacific Clinical Practice Guidelines for Hepatocellular Carcinoma, a naghị akwado iji AFP mee ihe. uru nchoputa dị elu na HCC.13 Tụnyere biopsy anụ ahụ, biopsy nke mmiri na-ebute ụzọ na-achọpụta metabolites metụtara tumor na mmiri ahụ (ọbara, mmiri mmiri, mmiri pleural, mmiri mmiri cerebrospinal, ma ọ bụ mmamịrị) ma ọ naghị emetụta anụ ahụ.14 N'ịgbakwụnye, biopsies mmiri mmiri nwere ike igosipụta njirimara ọjọọ adịghị na anụ ahụ bụ isi.15 A kabeghị nwale biopsies mmiri mmiri na omume ụlọọgwụ maka ụdị etuto ahụ niile, mana ikike ịchọpụta ọrịa kansa na-adọta uche ndị ọkà mmụta oncologists.16 Mmiri mmiri mmiri nwere ike ịchọpụta mkpụrụ ndụ tumor na-ekesa (CTCs), DNA tumor na-ekesa (cDNA), na-ekesa RNA efu (ecRNA), na exosomes.N'isiokwu a, anyị ga-atụle njirimara, ọrụ, na ntinye nke usoro biopsy mmiri dị iche iche na nyocha mmalite nke ndị otu HCC nwere nnukwu ihe ize ndụ.
DNA Extracellular (cfDNA) n'ime ọbara sitere na ndị nwere ahụike bụ nke mbụ kọwara na 1948 site n'aka Mandel et al.17 cfDNA bụ iberibe DNA na-enweghị mkpụrụ ndụ ihe dịka 160-180 bp n'ogologo, sitere na lymphocytes na mkpụrụ ndụ myeloid.ctDNA bụ mpempe DNA dị iche iche nke mkpụrụ ndụ tumo weputara n'ime ọbara dị n'akụkụ, nke na-anọchite anya ozi genomic nke mkpụrụ ndụ tumo mgbe ụfọdụ usoro pathophysiological, gụnyere necrosis, apoptosis, na excretion.Oke ctDNA na mkpokọta cfDNA na-adịgasị iche n'ụdị etuto ahụ, a na-akọkwa iberibe cDNA na-adịkarị obere karịa 167 bp n'ogologo.18 Nnyocha Underhill gosiri na iberibe cfDNA na-adịkarị mkpụmkpụ karịa cfDNA nkịtị.19 Tụnyere ndị nwere ahụike, ngụkọta ogologo nke cfDNA dị n'ọbara nke ndị ọrịa kansa dị mkpụmkpụ, yabụ enwere ike iji cfDNA dị ka ihe ngosi nyocha nyocha mbụ.Ịba ụba nke ụfọdụ akụkụ nke ogologo iberibe cfDNA nwere ike imezi nchọpụta cDNA jikọtara ya na etuto siri ike na-abụghị metastatic.Nnyocha egosila na a na-ahụ ctDNA n'ihe karịrị 75% nke pancreatic dị elu, eriri afọ, eriri afo, eriri afọ, imeju, ovarian, ara, melanoma, na ọrịa isi na olu.20,21 Otú ọ dị, ọnụ ọgụgụ ctDNA n'ime ọbara na-adabere na ọnọdụ nke etuto ahụ.22 N'ime nnyocha Bettegoud mere, a chọpụtara na ndị ọrịa nwere colorectal, ara, imeju, akpa ume, na ọrịa prostate na-enwe ọkwa dị elu nke cDNA n'ọbara ha karịa ọrịa cancer ndị ọzọ.N'ụzọ dị iche, na ndị ọrịa nwere ọrịa kansa ọnụ, ọrịa kansa pancreatic, ọrịa kansa afọ, na glioma, ntinye cDNA n'ime ọbara dị ala.iri abụọ na otu
N'ihi na ctDNA nwere otu mmụgharị mkpụrụ ndụ ihe nketa dị ka mkpụrụ ndụ tumor bụ isi, enwere ike iji cDNA chọpụta mmụgharị dị iche iche nke tumor na mgbanwe epigenetic, gụnyere methylation, hydroxymethylation, otu nucleotide dị iche iche, na ngbanwe nọmba.iri abụọ na atọ
DNA methylation bụ otu n'ime mgbanwe epigenetic na-emekarị na-ebute mbelata mkpụrụ ndụ ihe nketa.E jiri ya tụnyere mkpụrụ ndụ nkịtị, enwere ọdịiche dị na ọkwa methylation nke mkpụrụ ndụ tumor cell genome, karịsịa na methylation nke mkpụrụ ndụ ihe nketa tumor, nke a pụrụ ịchọpụta na mmalite oge, na-atụ aro na mgbanwe na DNA methylation nwere ike ịbụ ihe na-egosi mmalite. nchọpụta nke tumorigenesis.Mkpụrụ ndụ ihe nketa na-egbochi Tumor jikọtara ya na HCC nwere ike ime ka onye na-akwalite methylation kwụsị ọrụ, si otú ahụ na-akpali tumorigenesis.24 DNA methylation bụ ihe nrịbama dị mma maka nchọpụta mmalite nke etuto ahụ n'ihi nkọwa anụ ahụ ya, nchọpụta, na nnwere onwe nke afọ.Na mgbakwunye, DNA methylation bụ ihe a na-ahụkarị ma e jiri ya tụnyere mmụgharị somatic n'ihi na enwere ọtụtụ mpaghara ebumnuche yana ọtụtụ saịtị CpG gbanwere na mpaghara ọ bụla nke genome ebumnuche.25 Na mgbakwunye na ọtụtụ saịtị CpG, a chọpụtala ọnụ ọgụgụ dị ukwuu nke hypermethylated loci na ctDNA na DBX2, THY1, MT1M, INK4A, VIM, FBLN1, na RGS10.26 Xu et al.Ntụnyere ihe nlele cfDNA sitere na ndị ọrịa 1098 HCC na njikwa ahụike 835 bụ mkpụrụ ndụ ihe nketa jikọtara ya na HCC ka achọpụtara na ọ na-emekọrịta ihe na ntinye aka cDNA methylation plasma kwekọrọ.25 Dabere na nyocha ụlọ nyocha, e mepụtara ihe atụ amụma nke nwere 10 methylation markers nwere uche na nkọwa nke 85.7% na 94.3%, n'otu n'otu, na akara ndị a na-ejikọta nke ọma na ụbụrụ ụbụrụ, ọkwa ụbụrụ, na nzaghachi ọgwụgwọ.Nsonaazụ ndị a na-egosi na iji cDNA methylation markers nwere nnukwu nkwa na nchoputa, nlekota na prognosis nke HCC.N'ụdị methylation nke nwere mkpụrụ ndụ ihe nketa methylated atọ (APC, COX2, RASSF1A) na otu miRNA (miR203) nke Lu et al27 gosipụtara, nghọta na nkọwapụta nke ụdị 27 maka ịchọpụta HBV metụtara HCC bụ ihe atụ.80%Na mgbakwunye, ihe nlereanya ahụ nwere ike ịchọpụta 75% nke ndị ọrịa HCC na-achọpụtaghị na ọkwa AFP nke 20 ng/mL.Mkpụrụ ndụ ihe nketa maka ezinụlọ ngalaba Ras 1A protein (RASSF1A) bụ usoro DNA na-emegharị ugboro ugboro na genome mmadụ.Araujo et al.kwubiri na hypermethylation nke onye na-akwalite RASSF1A nwere ike ịbụ ihe bara uru biomarker maka nyocha mbụ nke HCC na ihe mgbaru ọsọ molekul maka ọgwụgwọ epigenetic.28 N'otu nyocha, a chọtara hypermethylation serum RASSF1A na 73.3% nke ndị ọrịa nwere HCC.29 Ihe nucleotide gbakọrọ ogologo 1 (LINE-1) bụ onye ogbugbo retrotransposition ọzọ na-arụsi ọrụ ike.Achọpụtara Hypomethylation nke LINE-1 na DNA nke 66.7% nke ihe nlele serum HCC ma jikọta ya na nlọghachi azụ n'oge na ndụ na-adịghị mma mgbe radical resection.29 Hypermethylation bụ usoro mkpụrụ ndụ ihe nketa na-arụ ọrụ pụrụ iche na mmepe nke imeju imeju na HCC.30 N'ụzọ dị iche, hydroxymethylation bụ usoro demethylation nke na-eme ka mkpụrụ ndụ maliteghachi na nkwupụta, na nchọpụta nke ngwaahịa 5-hydroxymethylcytosine (5-hmC) na usoro a nwere ike iji chọpụta etuto ahụ.Methylation na hydroxymethylation nke cDNA jikọtara ya na tumorigenesis ma nwee ike itinye aka na nyocha mbụ nke HCC.N'ime nyocha nke isiokwu 2554, a chọtara 31 genome-wide 5-hmCs na cfDNA samples, na mkpụrụ ndụ ihe nketa 32 chọpụtara site na iji usoro 5-hmC tụnyere ndị ọrịa HCC na ndị nwere nnukwu ihe ize ndụ dị ka ndị nwere ọrịa na-adịghị ala ala.Ụdị nchọpụta nke ọrịa imeju.na cirrhosis.Ihe nlereanya a dị elu karịa AFP n'ịmata ọdịiche HCC na anụ ahụ na-abụghị ụbụrụ.
Mgbanwe dị na mpaghara nzuzo nwere ike iduga nhụsianya nke ederede, nke nwere ike ibute mgbanwe na usoro protein na n'ikpeazụ kansa.Otu nucleotide dị iche iche bụ ihe nrịbama genomic dị mkpa maka nyocha mbụ etuto ahụ n'ihi ntụkwasị obi anụ ahụ dị elu yana nnukwu etuto na nkọwapụta anụ ahụ.Ọtụtụ ọmụmụ metụtara HCC na-eji usoro ọgbọ na-abịa (NGS) maka exome na usoro genome dum nke ọrịa kansa achọpụtala mkpụrụ ndụ ihe nketa cellular dị ka TP53 na CTNNB1, yana ọtụtụ gụnyere ARID1A, MLL, IRF2.Mkpụrụ ndụ ihe nketa ọhụrụ ahụ, ATM, CDKN2A, FGF19, PIK3CA, RPS6KA3 na JAK1 na-egosi ọnụego ngbanwe na-agafeghị oke. Nyocha ọrụ mkpụrụ ndụ ihe nketa na-egosi na mgbanwe na nhazigharị chromatin, Wnt / β-catenin na ntụgharị akara JAK / STAT, ụzọ okirikiri P53-cell, ndị na-eme mgbanwe epigenetic, ụzọ nrụgide oxidative, ụzọ PI3K / AKT / MTOR na RAS / RAF / Ụzọ MAPK kinase na-arụ ọrụ dị mkpa na HCC oncogenesis.32,33 N'ime nnyocha e mere na-achọpụta mgbanwe ndị metụtara tumor, Huang et al chọpụtara na ugboro ole mmụgharị ndị metụtara tumor na-adabere na ctDNA bụ 19.5%, na kpọmkwem bụ 90% .34 Tụkwasị na nke ahụ, ndị ọrịa nwere ahụmahụ mbuso agha vaskụla nwere ike inwe mmụgharị ctDNA (P=0.041) na ndụ dị mkpụmkpụ na-enweghị nlọghachi (P<0.001). Nyocha ọrụ mkpụrụ ndụ ihe nketa na-egosi na mgbanwe na nhazigharị chromatin, Wnt / β-catenin na ntụgharị akara JAK / STAT, ụzọ okirikiri P53-cell, ndị na-eme mgbanwe epigenetic, ụzọ nrụgide oxidative, ụzọ PI3K / AKT / MTOR na RAS / RAF / Ụzọ MAPK kinase na-arụ ọrụ dị mkpa na HCC oncogenesis.32,33 N'ime nnyocha e mere na-achọpụta mgbanwe ndị metụtara tumor, Huang et al chọpụtara na ugboro ole mmụgharị ndị metụtara tumor na-adabere na ctDNA bụ 19.5%, na kpọmkwem bụ 90% .34 Tụkwasị na nke ahụ, ndị ọrịa nwere ahụmahụ mbuso agha vaskụla nwere ike inwe mmụgharị ctDNA (P=0.041) na ndụ dị mkpụmkpụ na-enweghị nlọghachi (P<0.001).Nyocha ọrụ mkpụrụ ndụ ihe nketa na-egosi na mgbanwe na chromatin remodeling, Wnt / β-catenin na JAK / STAT na-egosi, P53 cell cell ụzọ, epigenetic modifiers, oxidative stress ụzọ, PI3K / AKT / MTOR ụzọ, na RAS / RAF / MAPK kinase ụzọ egwu egwu. ọrụ dị oke egwu na HCC tumorigenesis.32,33 N'ime nchọpụta nke chọpụtara mgbanwe ndị metụtara tumor, Huang et al.chọpụtara na ugboro ole mmụgharị metụtara tumor na-adabere na ctDNA bụ 19.5% na nkọwa ya bụ 90%..34. .34 Na mgbakwunye, ndị ọrịa nwere mbuso agha vaskụla nwere ọtụtụ mmụgharị cDNA (P = 0.041) na ndụ na-enweghị ọrịa dị mkpụmkpụ (P <0.001).Nyocha ọrụ nke mkpụrụ ndụ ihe nketa na-ekpughere chromatin remodeling, Wnt / β-catenin na JAK / STAT na-egosi, ụzọ P53 cell cell path, epigenetic modifiers, the oxidative stress way, PI3K/AKT/MTOR ụzọ, na RAS/RAF/MAPK. ụzọ kinase na-arụ ọrụ dị oke mkpa na oncogenesis nke HCC. 32,33 项 项 项 项 项 检测 相关 相关 肿瘤 相关 等 发现 发现 发现 依赖于 Ctdna 的 19.5%, 特异性 此外 90% .34 侵犯 更 有 可能 可能 Ctdna突变(P=0.041)和更短的无复发生存期(P<0.001)。 32.33 项 检测 在 检测 检测 检测 相关 等 肿瘤 肿瘤 肿瘤 相关 Ctdna 的 为 19.5%, 特异性 经历 90% .34 发生 Ctdna 突变 (p = 0.041) 和短的无复发生存期(P<0.001)。32,33 N'ime nnyocha nke chọpụtara mgbanwe ndị metụtara tumor, Huang et al.chọpụtara na ngbanwe ndị metụtara tumor bụ 19.5% dabere na cDNA na nkọwa nke 90% 34. Tụkwasị na nke ahụ, ndị ọrịa na-ebute mwakpo vaskụla nwere ike ịmalite cDNA.мутация (P = 0,041) na более короткая безрецидивная выживаемость (P <0,001). mutation (P=0.041) na ndụ na-enweghị ọrịa dị mkpụmkpụ (P<0.001).Mkpụrụ ndụ ihe nketa HCC ọzọ a na-ahụkarị bụ TP53, nke nwere ngbanwe nke ihe karịrị 30%.Nnyocha egosiwo na ugboro ole mmụgharị TP53 na ctDNA n'ọbara na mmamịrị sitere na 5% ruo 60%.35 Nnyocha Johan gosiri na ctDNA mutation spectrum na mbubreyo HCC nwere mmụgharị yiri nke ahụ na HCC n'oge, gụnyere onye nkwalite TERT (51%), TP53 (32%), CTNNB1 (17%), PTEN (8%), mmụgharị na AXIN1 ., ARID2, KMT2D na TSC2 (6% nke ọ bụla).36 β-catenin (CTNNB1) oncogene na-arụ ọrụ dị mkpa na ụzọ akara Wnt.Onye na-ahụ maka ntụgharị CTNNB1 nwere ike ịkwalite okwu mkpụrụ ndụ ihe nketa, nke nwere ike iduga mgbasawanye cell, mgbochi nke apoptosis, na angiogenesis.CTNNB1 nwekwara ike na-emekọrịta ihe na TERT iji kpalite mgbanwe hepatocyte.33 A na-agbanwekarị onye na-akwalite TERT n'ụfọdụ etuto siri ike.Mgbanwe na TERT, otu n'ime mgbanwe mkpụrụ ndụ ihe nketa mbụ na mgbanwe ọjọọ nke HCC, nwere ike iduga na telomerase reactivation na hepatocytes cirrhotic ma nwee ike ịkwalite mmụba na igbochi ịka nká.Mgbanwe na 33-37 TERT nkwalite ka akọọrọ na ọ ga-eme na 59-90% nke ndị ọrịa nwere nodules imeju na-amụba na mmalite HCC ma jikọta ya na nlanarị.38
Mgbanwe nọmba nnomi (CNA) bụ ihe dị mkpa n'ụdị mmụgharị somatic.Nnyocha egosila na ibu zuru ebe niile na nke CNA bụ mbinye aka genomic nwere ike ibu amụma ntinye mgbochi ọrịa tumor na mwepu na ụdị ọrịa kansa ụfọdụ.39 Ihe nrịbama ntinye nke na-arụ ọrụ, ọrụ cytolytic dị elu, nnukwu mbufụt na akara mkpụrụ ndụ ihe nketa jikọtara na ngosipụta antigen na HCC.Nyocha nke nhazi data nke otu nucleotide polymorphisms na isiokwu 477 kpughere ibu dị ala na CNS.N'ụzọ dị iche, etuto ahụ na-adịghị akwụsi ike nke chromosomally nwere nnukwu ibu CNA gosipụtara ihe ịrịba ama nke ịjụ mgbochi ọrịa ma jikọta ya na mmụba, nrụzi DNA, na arụ ọrụ TP53.Xu et al.gosiri na otu HCC nwere ọnụ ọgụgụ CNA dị elu karịa otu ọrịa imeju na-adịghị ala ala.40 N'iji usoro genome zuru oke nke otu cell, ahụrụ na CNA na-apụta n'oge hepatocarcinogenesis ma na-adịgide adịgide n'oge ọganihu tumor.41 Chung et al.chọpụtara na ọkwa cfDNA dị elu nke ukwuu na ndị ọrịa HCC yana na genome-wide CNAs na cfDNA bụ ihe nrịbama prognostic dị mkpa na ndị ọrịa HCC na-agwọ sorafenib.42 Ndị ọrịa nwere ibu CNA dị elu nwere ike inwe ọganihu ọrịa na ọnwụ karịa ndị nwere ibu CNA dị ala.Ollerich et al.chọpụtara na enwere ike iji ndetu nọmba enweghị ike (CNI) iji nyochaa CNA na cfDNA nke ndị ọrịa kansa.Ha kwuru na ndị ọrịa nwere ọrịa kansa dị elu nwere akara CNI dị elu karịa otu njikwa, nke na-enyocha nzaghachi ndị ọrịa na usoro chemotherapy na immunotherapy.43 Nsonaazụ ndị a na-atụ aro na CNA ndị a na-ahụ n'ụdị mmiri mmiri biopsy nwere ike bụrụ ihe ngosipụta amụma na ndị ọrịa nwere ọrịa kansa dị elu.HCC na ndabere nke usoro ọgwụgwọ.
Ugbu a, ụzọ ndị a na-eji chọpụta ctDNA nwere ike kewaa n'ime ụzọ ezubere iche na nke na-abụghị nke ezubere iche.Na nkenke, ụzọ ezubere iche dị ka mmeghachi omume chain polymerase dijitalụ (dPCR), BEAMing dijitalụ PCR, Amplification Refractory Mutation System-PCR, Capp-Seq na Tam-Seq na-enwe mmetụta nke ukwuu maka mkpụrụ ndụ ihe nketa ebugoro.Ụzọ ndị na-apụ apụ dị ka usoro mkpụrụ ndụ ihe nketa dum na NGS na-enye echiche zuru oke banyere ọdịdị ala genomic dum.44 Tụnyere akụkụ ezubere iche, usoro genome dum nwere ike ịchọpụta ọ bụghị naanị ngbanwe ntụzịaka na ntinye, kamakwa nhazigharị yana ngbanwe ọnụọgụgụ.prognosis, na CTC na cfDNA bụ ihe ngosi dị mma nke enwere ike iji maka nleba anya siri ike nke HCC.45 Na mgbakwunye, nyocha cfDNA nwere ike ịba uru karịa n'ịchọpụta HCC.Yan et al.gosiri na cfDNA na plasma nke ndị ọrịa nwere HCC dị elu karịa ndị ọrịa nwere fibrosis imeju yana njikwa ahụike.Tụnyere AFP, a na-atụ anya na ctDNA ga-abụ akara nyocha kacha mma maka mbido HCC.46 N'ime nyocha nke nyocha nke biopsies mmiri mmiri 47 nke nwalere cfDNA na protein n'ime ọnụ ọgụgụ mmadụ, egosiri na ha dị irè n'ichepụta ndị ọrịa nwere HCC na ndị ọrịa na-enweghị HCC.Na nchikota nke 331 ultrasound normal na AFP-negative ọrịa, uche na nkọwapụta nke cfDNA maka ịchọpụta HCC bụ 100% na 94%, n'otu n'otu, ya mere cDNA nwere ike chọpụta HCC na asymptomatic HBsAg seropositive ndị mmadụ.N'ime ọmụmụ Yeo48, a chọtara ọtụtụ ugboro (92.5%) nke hypermethylation nke onye nkwalite RASSF1A na ndị ọrịa nwere HCC.Na mgbakwunye, Xu et al.mepụtara usoro nyocha iji buo amụma HCC site na iji otu panel nke akara methylation akọwapụtara nke nwere nkọwapụta na nghọta nke 90.5% na 83.3%, n'otu n'otu.Ogwe ahụ na-enye ohere ka ndị ọrịa nwere HCC dị iche na ndị ọrịa nwere ọrịa imeju ndị ọzọ, nke dị mma karịa AFP.Ha chọpụtakwara na njikwa nkịtị nke nwalere nke ọma nwere ike ịnwe ihe ize ndụ maka HCC, dị ka ọrịa HBV ma ọ bụ akụkọ ihe mere eme nke ịṅụ mmanya.25 Anyị na-eche na ihe ize ndụ dị elu maka HCC nwere ike ịkwalite hypermethylation nke cfDNA, nke na-enye aka na ọganihu nke HCC, ya mere cfDNA nwere ike ịrụ ọrụ dị mkpa na nyocha maka otu ndị nwere nnukwu ihe ize ndụ.Cai et al.chịkọta ọnụ ọgụgụ zuru oke nke mmụgharị ctDNA ma nye atụmatụ siri ike maka ịlele ibu akpụ na ndị ọrịa.49 Usoro a nwere ike ịchọpụta tumorigenesis nke etiti ọnwa 4.6 tupu mgbanwe onyonyo wee gosipụta arụmọrụ nchọpụta dị elu ma e jiri ya tụnyere serum biomarkers AFP, AFP-L3, na PIVKA-II.Egosiputa uru nchoputa nke nyocha cDNA mgbe nyocha onyonyo adighi, ya mere ule cDNA bara uru na nchoputa nke HCC n'oge n'ime otu ndi di elu.N'oge na-adịbeghị anya, ndị ọkà mmụta sayensị jiri nkà na ụzụ NGS nyochaa ihe na-egosi ọdịiche dị iche iche nke mkpụrụ ndụ ihe nketa (gụnyere 5-hydroxymethylcytosine, 5'-motif, fragmentation, nucleosome trace, HIFI) na 3204 clinical samples na cfDNA.Ụdị HIFI 50 emezigharịrị nwere ụgbọ oloko atọ kwụụrụ onwe ya, ule, na usoro nnwale gosipụtara ịkpa oke kwụsiri ike na ntụkwasị obi n'etiti ndị HCC na ndị na-abụghị HCC nwere 95.79% na 95.42% nhụsianya n'ụdị ule na nnwale HCC, n'otu n'otu.Mmekọ nwoke na nwanyị bụ 95.00% na 97.83%, n'otu n'otu.Uru nchoputa nke usoro HIFI dị elu karịa nke AFP na ịmata ọdịiche HCC na cirrhosis.Na mgbakwunye, a na-ejikwa ctDNA na ọgwụgwọ ịwa ahụ.Atsushi et al.kpebisiri ike na ọkwa nke ctDNA tupu ịwa ahụ n'ime ndị ọrịa nwere HCC wee chọpụta na ọnụọgụ nlọghachi azụ na ọnụọgụ metastasis extrahepatic na cDNA dị mma dị elu karịa na cDNA ọjọọ, na ọkwa cDNA jikọtara nke ọma.na ọganihu etuto ahụ.N'ịbụ onye na-ahụ maka biomarker nke ukwuu, ctDNA nwere ike ibu amụma ike HCC ịwakpo arịa.Wang et al.rụrụ usoro genome dum nke ndị ọrịa 46 nwere HCC, yana nyocha dị iche iche gosipụtara na uru ọnụ ụzọ nke ugboro ole cDNA dị iche iche maka mbuso agha n'ime microvessels bụ 0.83%, uche 89.7% na nkọwapụta 80.0%.ihe ize ndụ nke onwe maka mwakpo microvascular na HCC resectable, na-atụ aro na cDNA nwere ike inye aka na-eduzi ọgwụgwọ kacha mma.Na mmechi, ctDNA na-etinye aka na nsonazụ na mmepe nke HCC na enwere ike iji ya mee nyocha mmalite, nyocha ịwa ahụ, na nlekota ọrịa.
CTC bụ mkpụrụ ndụ ọjọọ ewepụtara site na etuto isi ma ọ bụ metastases nke metastasize ruo n'ọbara.Mkpụrụ ndụ Tumor na-ezobe matrix metalloproteinases (MMPs), nke na-akụda akpụkpọ ahụ okpuru ulo, na-ekwe ka mkpụrụ ndụ tumo banye n'ọbara na arịa lymph.Otú ọ dị, a na-ekpochapụ ọtụtụ CTC ngwa ngwa site na anoikis, ọgụ mgbochi, ma ọ bụ nrụgide siri ike.53 Mgbanwe nke epithelial-mesenchymal (EMT) na-enye ohere ka CTC kewapụrụ ngwa ngwa site na anụ ahụ bụ isi tumor, wakpo capillaries, ma nweta nnukwu ndụ ndụ, metastasis, invasiveness, na mgbochi ọgwụ.Nnyocha egosiwo na e nwere nnukwu heterogeneity n'etiti mkpụrụ ndụ etuto dị iche iche na etuto metastatic bụ isi.Ya mere, nyocha CTC nwere ike iduga nghọta zuru oke nke mkpụrụ ndụ tumor cell heterogeneity.54
Ihe nrịbama a kapịrị ọnụ maka CTC ndị metụtara HCC gụnyere glypican-3 (GPC3), asialoglycoprotein receptor (ASGPR), molecule cell adhesion molecule (EpCAM) na ihe nrịbama metụtara cell dị ka CD44, CD90, 55 na intercellular adhesion molecule 1 (ICAM1e).) .56 Ihe nrịbama GPC3 bụ protein mechiri emechi sel nke a na-eji eme ihe maka nyocha ọrịa na njirimara nke HCC.57 Ngosipụta nke GPC3 na-adịkarị na mkpụrụ ndụ tumor HCC nwere ọdịiche dị n'etiti na nke dị ala ma na-akwalite ọpụpụ extrahepatic;na mgbakwunye, ọnụnọ nke GPC3+ CTC na-egosi HCC metastatic.58 ASGPR bụ protein transmembrane egosipụtara naanị n'elu hepatocytes ma gosipụta ya nke ukwuu na HCC dị iche iche.EpCAM bụ otu n'ime protein ndị metụtara akpụkpọ ahụ na-ejikarị ejide CTC.Achọpụtara EpCAM dị ka ihe nrịbama elu nke mkpụrụ ndụ HCC nwere njirimara sel stem,59 nke jikọtara ya na akụkụ dị iche iche nke clinicopathological nke HCC, dị ka mwakpo vaskụla, nyocha ọkwa AFP, na ọkwa dị elu nke ọrịa imeju na ụlọ ọgwụ Barcelona (BCLC).60 CTC EMT phenotype bụ nnukwu metastatic.Usoro 54 EMT dị na CTC na-akwalite metastasis HCC.Ngosipụta nke akara EMT dị ka vimentin, twist, E-box zinc finger binding (ZEB) 1, ZEB2, snail, slug, na E-cadherin na-amụba na CTC nke imeju na-enweta site n'aka ndị ọrịa HCC.58 Sistemu CanPatrol™ nke Cheng [61] mebere nkewa CTC n'ime obere obere phenotypic atọ dabere na akara nke egosipụtara nke ukwuu: epithelial phenotype (EpCAM, CK8/18/19), mesenchymal phenotype (vimentin, coiled), na ụdị phenotypes agwakọta.N'ime ndị ọrịa 176, ngụkọta CTC dị elu karịa AFP n'ichepụta HCC na ọrịa imeju na-adịghị mma.Ụkpụrụ AUC maka mkpokọta CTC, AFP na mkpokọta CTC na AFP bụ 0.774 (95% CI, 0.704-0.834), 0.669 (95% CI, 0.587-0.750), na 0.821 (95% CI, 0.756-0.8) ).), n'otu n'otu.Nhazi CTC dabere na EMT nwere ike ibu amụma nchoputa HCC, nlọghachite n'oge, metastasis, na obere oge n'ozuzu ya.
Ugbu a, ụzọ maka ịchọpụta CSC gụnyere usoro anụ ahụ na usoro ndu.Ụzọ anụ ahụ, nke a na-akpọkarị ịba ọgaranya dabere na ihe ndị dị ndụ, na-adabere na njirimara anụ ahụ nke CSC, dị ka nha, njupụta, ụgwọ, njem na nrụrụ.Dabere na akụrụngwa anụ ahụ, enwere ụzọ dị iche iche dị ka sistemu nke dabere na filtration, dielectrophoresis, wdg. Nke ikpeazụ, nke a makwaara dị ka mmụba nke immunoaffinity, dabere na njikọ antigen-antibody, ebe ọ bụ na usoro ahụ na-eji ọgwụ mgbochi megide tumor-kpọmkwem biomarkers. dị ka EpCAM, ASGPR, onye na-anabata ihe na-eto eto epidermal 2 (HER2), prostate kpọmkwem antigen (PSA), pancytokeratin mmadụ (P-CK) na carbamoyl phosphate synthase 1 (CPS1).62 Ụdị ọzọ, nke a na-akpọ usoro enweghị-enrichment, na-eji cytometry eruba iji mata ọdịiche dị n'etiti CTC site na leukocytes dabere na oke nuklia-na-cytoplasmic dị elu na nha.Ugbu a, naanị ule FDA kwadoro maka nchọpụta nke CTC bụ usoro Cell-Search™, nke na-eji akara elu cell EpCAM. Otú ọ dị, nchọpụta CTC jikọtara ọnụ nwere ike ime ka ọnụ ọgụgụ dị elu dịkwuo elu.54 Ngwakọta ọgwụ mgbochi megide ASGPR na CPS1 nwetara ọnụọgụ nchọpụta CTC nke 91% na ndị ọrịa HCC.63 Zhang et al jiri CTC-Chip nwere ọgwụ mgbochi megide ASGPR, P -CK na CPS1, na ndị ọrịa HCC dị iche na ndị nwere ọrịa imeju na-adịghị mma ma ọ bụ ọrịa cancer na-abụghị HCC na ọnụ ọgụgụ nke 100%.64 Nnyocha nke Wang chọpụtara EpCAM+ CTC na 60% nke ndị ọrịa 42 HCC wee chọpụta njikọ dị ịrịba ama n'etiti ma ndị ahụ dị mma. ọnụ ọgụgụ na ọnụ ọgụgụ nke CTC na TNM stage.65 Guo et al chọpụtara na a na-ebuli akara PCR nke CTC na 125/171 (73%) ndị ọrịa nke ọkwa AFP bụ <20 ng/mL nwere mmetụta nke 72.5% na a. kpọmkwem nke 95.0%, ma e jiri ya tụnyere 57.0% na 90.0% maka AFP na nkwụsị nke 20 ng/mL.66 Njikọ nke AFP na CTC nwere ike ime ka nchọpụta HCC dịkwuo mma.45 Ekwenyere na CTC nwere uru karịa AFP na mmalite nyocha nke otu. na nnukwu ihe ize ndụ maka HCC. Otú ọ dị, nchọpụta CTC jikọtara ọnụ nwere ike ime ka ọnụ ọgụgụ dị elu dịkwuo elu.54 Ngwakọta ọgwụ mgbochi megide ASGPR na CPS1 nwetara ọnụọgụ nchọpụta CTC nke 91% na ndị ọrịa HCC.63 Zhang et al jiri CTC-Chip nwere ọgwụ mgbochi megide ASGPR, P -CK na CPS1, na ndị ọrịa HCC dị iche na ndị nwere ọrịa imeju na-adịghị mma ma ọ bụ ọrịa cancer na-abụghị HCC na ọnụ ọgụgụ nke 100%.64 Nnyocha nke Wang chọpụtara EpCAM+ CTC na 60% nke ndị ọrịa 42 HCC wee chọpụta njikọ dị ịrịba ama n'etiti ma ndị ahụ dị mma. ọnụ ọgụgụ na ọnụ ọgụgụ nke CTC na TNM stage.65 Guo et al chọpụtara na a na-ebuli akara PCR nke CTC na 125/171 (73%) ndị ọrịa nke ọkwa AFP bụ <20 ng/mL nwere mmetụta nke 72.5% na a. kpọmkwem nke 95.0%, ma e jiri ya tụnyere 57.0% na 90.0% maka AFP na nkwụsị nke 20 ng/mL.66 Njikọ nke AFP na CTC nwere ike ime ka nchọpụta HCC dịkwuo mma.45 Ekwenyere na CTC nwere uru karịa AFP na mmalite nyocha nke otu. na nnukwu ihe ize ndụ maka HCC.Otú ọ dị, nchọta njiko nke CTC na-adabere na akara nwere ike ịbawanye pasent nke nsonaazụ dị mma.54 Ngwakọta nke mgbochi ASGPR na CPS1 na-enweta ọnụọgụ nchọpụta CTC nke 91% na ndị ọrịa nwere HCC.63 Zhang et al.jiri CTC-Chip nwere ọgwụ mgbochi megide ASGPR, P-CK na CPS1, ma meekwa ka ndị ọrịa nwere HCC dị iche na ndị nwere ọrịa imeju na-adịghị mma ma ọ bụ ndị na-abụghị HCC na ọnụego 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 agba. ugboro na ọnụ ọgụgụ nke CTC na TNM ogbo.65 Guo et al chọpụtara na PCR ewepụtara na CTC dị elu na 125/171 (73%) ndị ọrịa nwere ọkwa AFP <20 ng/mL nwere mmetụta nke 72.5% na nkọwapụta. 95.0% tụnyere 57.0% na 90.0% maka AFP na ọkwa nkwụsị nke 20 ng / ml.66 Njikọ nke AFP na CTC nwere ike ime ka nchọpụta nke HCC dịkwuo mma. otu.nwere nnukwu ihe ize ndụ nke HCC.Agbanyeghị, nchọta njikọta nke CTC nwere ike ịbawanye pasentị nke nsonaazụ dị mma.54 Ngwakọta nke mgbochi ASGPR na ọgwụ mgbochi CPS1 nwetara ọnụọgụ nchọpụta 91% CTC na ndị ọrịa nwere HCC.63 Zhang et al.ejiri CTC ibe nwere ọgwụ mgbochi megide ASGPR, P-CK na CPS1 yana ndị ọrịa nwere HCC nwere ọrịa imeju na-adịghị mma na ndị na-abụghị HCC nwere 100%.64 Ọmụmụ Wang chọpụtara 60% nke EpCAM+ CTC n'ime ndị ọrịa 42 HCC wee chọpụta njikọ dị n'etiti ihe omume na ọnụ ọgụgụ nke CTC na ọkwa TNM. 65 Guo 等人发现,在AFP 水平<20 ng/mL 的125/171 (73%) 名患者中, CTC值为20 ng/mL 时的特异性为57.0% 和90.0%. 65 gua 等 发现 20 ng / ml 的 125/171 (73%) 评分, CTC 衍生, CTC 衍生 ::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 截止 20ng / ml 时 的 57.0% 和 90.0%.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. chọpụtara na na 125/171 (73%) ndị ọrịa nwere ọkwa AFP <20 ng/mL, ụkpụrụ PCR sitere na CTC na-ebuli elu site na uche nke 72.5% na nkọwapụta nke 95.0%, ebe AFP nọ na nkọwapụta. bụ 20ng/ml.ml bụ 57.0% na 90.0%.66 Ngwakọta ORP na CTC na-eme ka nchọpụta HCC dịkwuo mma.A na-eche na CTC 45 dị elu karịa AFP na mbido nyocha nke ọnụ ọgụgụ HCC nwere nnukwu ihe ize ndụ.Ya mere, maka ndị otu HCC dị mma na nke nwere nnukwu ihe ize ndụ, a ga-ejikọta ule CTC na ultrasound na nchọpụta AFP.Otú ọ dị, a na-ewere CTC dị ka ndị na-ebu amụma banyere metastasis tumor na nlọghachi azụ, na nchọpụta nke CTC adịghị akwado onwe ya dị ka ngwá ọrụ nyocha.62 Ya mere, CTC nwere ike ije ozi dị ka ihe nrịbama biomarker ka mma karịa akara ndị ọzọ ejiri ugbu a. Zhou et al chọpụtara na ndị ọrịa nwere ọnụ ọgụgụ dị elu nke EpCAM + CTCs na sel T na-achịkwa gosipụtara ihe ize ndụ dị elu nke ịmaliteghachi nlọghachi nke HCC, karịa ndị nwere ọnụ ọgụgụ dị ala nke CTC, na-enwe nlọghachi nke 66.7% vs 10.3% (P <0.001) .67 Otu ihe ọmụmụ yiri nke Zhong et al.68 na-akọ na mgbakwunye, Qi chọpụtara na 101 nke ndị ọrịa 112 (90.81%) nwere HCC, gụnyere ndị nwere ọrịa mmalite, dị mma maka CTC na na a chọtara obere HCC nodules mgbe 3 gasịrị. ruo ọnwa 5 nke nleba anya. Zhou et al chọpụtara na ndị ọrịa nwere ọnụ ọgụgụ dị elu nke EpCAM + CTCs na sel T na-achịkwa gosipụtara ihe ize ndụ dị elu nke ịmaliteghachi nlọghachi nke HCC karịa ndị nwere ọnụ ọgụgụ dị ala nke CTC, na nkwụghachi azụ nke 66.7% vs 10.3% (P <0.001) .67 A. Zhong et al.68 kwukwara, Qi chọpụtara na 101 n'ime ndị ọrịa 112 (90.81%) nwere HCC, gụnyere ndị nwere ọrịa mmalite, dị mma maka CTC na na ahụrụ obere HCC nodules mgbe 3 gachara. Ọnwa 5 nke nleba anya. Чжоу na 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 chọpụtara na ndị ọrịa nwere elu EpCAM + CTCs na sel T na-achịkwa nwere ihe ize ndụ dị elu nke nlọghachite HCC karịa ndị nwere CTC dị ala, na ọnụ ọgụgụ nlọghachi nke 66.7% vs 10.3% (P <0.001) 67.Otu ihe omumu nke Zhong et al mere.68. Tụkwasị na nke ahụ, Qi chọpụtara na 101 n'ime ndị ọrịa 112 (90.81%) nwere HCC, gụnyere ndị nwere ọrịa mbụ, nwere CTCs, nakwa na a chọtara obere HCC nodules mgbe ọnwa 3 ruo 5 gasịrị. Zhou 等, 与 CTC 数量 相比 患者 患者 和 c 和 细胞 数量 hcc 复发 风险 风险 更 更 更 为 为 为 为 66.7% (p <0.001). 等 等与 等 人 与 与 与 与 与 患者 患者 患者 患者 患者 患者 患者 和 和和 和 分别 分别 分别 分别 分别 分别 为 为 为 为 为 为 为 为 为 为 13% ( p <0.001) …………………………………………. Чжоу na 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.chọpụtara na ndị ọrịa nwere elu EpCAM + CTC na sel T na-achịkwa nwere ihe ize ndụ dị elu nke nlọghachite HCC ma e jiri ya tụnyere ndị ọrịa nwere CTC ole na ole, na ọnụ ọgụgụ nlọghachi nke 66.7% na 10.3%, n'otu n'otu (P <0.001).Zhong et al kọrọ otu ọmụmụ ihe ahụ.68 Na mgbakwunye, Qi chọpụtara na 101 n'ime ndị ọrịa 112 HCC (90.81%), gụnyere ndị ọrịa nwere ọrịa mbụ, nwere nsonaazụ CTC dị mma ma chọta obere HCC nodules mgbe nleta 3 gasịrị.Nleba anya ruo ọnwa 5.Ha hụkwara CTC n'ime ndị ọrịa iri na abụọ nwere ọrịa HBV na-adịghị ala ala wee hụ obere etuto HCC n'ime ọnwa ise n'ime ndị ọrịa 2 nwere CTC.69 Ya mere, enwere ike iji CTC mee amụma HCC, 70 mana enwere ike iji ha mee ihe mgbe niile dị ka ndị na-ebu amụma biomarkers.
Dịka cfDNA, a na-ewepụta cfRNA n'ime ọbara site na usoro dị iche iche.Ụmụ irighiri ihe ndị a dị n'ọbara dị n'akụkụ na-anọchi anya anụ ahụ nwere ọrịa kansa sitere na ya.Tụnyere akara nrịbama nke ụzọ anaghị emebi emebi achọpụtara, cfRNA na-achịkwa nke ọma karị, nke akọwapụtara anụ ahụ, yana ọtụtụ na gburugburu mpụga.Mkpa na nchoputa nke 71 miRNAs (miRNAs) na HCC ka akọpụtala n'ọtụtụ ọmụmụ.miRNA bụ endogenous RNA ndị na-abụghị koodu (ncRNA) nke na-ahazi ọrụ dị iche iche nke ndụ ndụ site na igbochi ntụgharị nke RNA ozi lekwasịrị anya (mRNA).miRNA dị n'ime ahụ apoptotic nke etinyere na exosomes, mana ha nwekwara ike jikọta protein na lipids na ọbara dị n'akụkụ ma enwere ike iji ya nyochaa HCC.microRNA na-etinye aka na imeju imeju, metabolism lipid, apoptosis, mbufụt, na mmepe nke HCC.72 Oncogenic miRNA dị ka miR-21, miR-155 na miR-221 bụ ndị amara nke ọma na HCC.Karịsịa, miR-21 na-arụ ọrụ dị mkpa na njikọ collagen na matrix extracellular na fibrosis ma na-akwalite hepatocarcinogenesis site na ịgbalite mkpụrụ ndụ hematopoietic.72,73 Tumor suppressor miRNA na HCC gụnyere miRNA-122, miRNA-29, ezinụlọ Let-7, na ezinụlọ miRNA-15.Ezinụlọ Let-7 nwere ọtụtụ miRNA ndị na-egbochi tumor nke na-elekwasị anya na ezinụlọ RAS.Ezinụlọ miR-15 gụnyere miR-15a, miR-15b, miR-16, miR-195 na miR-497, nke nwere usoro nkwado maka ụfọdụ mRNA.Na mgbakwunye, ogologo RNA ndị na-abụghị koodu (lncRNA) na RNA okirikiri (cirRNA) dịkwa mkpa maka nyocha mbụ nke HCC.lncRNA na-anọchi anya klaasị kachasị nke ncRNA, gụnyere mRNA dị ka ncRNA, ma na-etinye aka na pathogenesis nke ọtụtụ ọrịa mmadụ.LncRNA na-arụ ọrụ nchịkwa na microenvironment imeju na ọrịa imeju na-adịghị ala ala.74 CircRNA bụkwa klas nke ncRNA nwere ọtụtụ ọrụ na nhazi okwu mkpụrụ ndụ ihe nketa.N'oge na-adịbeghị anya, a na-ahụta circRNA dị ka ngwaọrụ nyocha maka HCC.
Mgbasa RNA efu nwere nkwụsi ike dị ịrịba ama, gụnyere iguzogide okpomọkụ, pH, na RNase, nke na-eme ka ikewapụ fnRNA na ọbara dị n'akụkụ ka ọ na-agwụ ike site na iji usoro RNA ọkọlọtọ.Ụzọ ndị a na-ejikarị agụnye NGS, microarray na RT-qPCR.NGS na-enye ohere ka a tụọ microRNAs n'ime genome niile.Otú ọ dị, usoro a dị oke ọnụ na nyocha adịghị ahazi.N'ụzọ dị iche, RT-qPCR adịghị ọnụ, na-amụba acids nucleic ngwa ngwa, ma na-enye ọtụtụ uru dị ka uche dị elu, izi ezi dị elu, oke ike sara mbara, yana chọrọ nlele ole na ole.Microarrays bụ usoro ọzọ a na-eji maka nchọpụta miRNA dabere na ngwakọ dị nro na nke akọwapụtara nke miRNA nwere ihe nyocha DNA agbakwunyere, 75 mana nyocha nke data microarray na-ewe oge.
Akọwo na-ekesa miR-122 na Let-7 nwere ike ịba uru n'ịchọpụta HCC n'oge n'ime otu dị oke egwu, akara nrịbama na ndị ọrịa nwere nodules premalignant metụtara HBV yana HCC mmalite.76 Cai et al.chọpụtara na ndị òtù ezinụlọ Let-7 (miR-92, miR-122, miR-125b, miR-143, miR-192, miR-16, miR-126, na miR-199a/b) nọ n'ihe ize ndụ nke na-adịghị ala ala HCC na ndị ọrịa nwere ịba ọcha n'anya.Ezinụlọ Let-7 nwere ike ije ozi dị ka onye na-ahụ maka ihe ndị na-ahụ maka ọgwụgwọ dị irè maka ịkọ mmepe nke HCC n'ime ìgwè ndị nwere nnukwu ihe ize ndụ jikọtara ya na ịba ọcha n'anya C. 77 miR-122 nwere ezigbo nchọpụta nchọpụta dị elu n'ịchọpụta mmalite HCC na ndị ọrịa nwere imeju imeju.78 Serum na-ekesa MiR-107 ka a tụlekwara n'oge mmalite nke HCC, 79 ma gosipụta ike dị mma na ndị mmadụ nwere nnukwu ihe ize ndụ.Zhou et al kọrọ na otu panel nke miRNAs (miR-122, miR-192, miR-21, miR-223, miR-26a, miR-27a na miR-801) nwere ike ịmata ọdịiche dị na HCC na ịba ọcha n'anya B (CHB) na cirrhosis. uche bụ 79.1% na 75%, na nkọwapụta 76.4% na 91.1%, n'otu n'otu.80 Na HCC metụtara HBV, anyị chọpụtara na ọkwa miR150 belatara nke ukwuu ma e jiri ya tụnyere ndị na-arịa ọrịa HBV na-adịghị ala ala na-enweghị HCC (nhụta 79.1%, nkọwapụta 76.5%).-224 buliri elu na HCC ma e jiri ya tụnyere njikwa ahụike, na nyocha nke obere ìgwè gosipụtara ọkwa dị elu na ndị ọrịa nwere HCC metụtara HBV.cirrhosis nke ịba ọcha n'anya B na ndị ọrịa HCC achọpụtara ihe nhazi ọkwa siRNA nwere siRNA asaa dị iche iche nwere ike ịchọpụta HCC na njikwa dị iche iche;Ogologo AUC n'oge nyocha mbụ dị mma karịa ndị ọrụ afọ ofufo AFP.Ha chọpụtara na miRNA anọ (miR-1972, miR-193a-5p, miR-214-3p, na miR-365a-3p) nwere ike ịmata ndị ọrịa nwere HCC na ndị ọrịa na-enweghị HCC.A na-ahụta miRNA ise na-emebiga ihe ókè (miR-122-5p, miR-125b-5p, miR-885-5p, miR-100-5p, na miR-148a-3p) nwere ike ibute ọrịa HBV na HCC, cirrhosis na CHB biomarkers, karịsịa. miR-34a-5p nwere ike ịbụ biomarkers maka imeju imeju, 85 ma nwee ike bụrụ ihe ndị nwere ike ime ihe maka nyocha mmalite nke HCC na ọnụ ọgụgụ ndị nwere nnukwu ihe ize ndụ.lncRNA kacha mụọ na HCC na-arụ ọrụ nke ukwuu na ọrịa kansa imeju (HULC).Ọmụmụ ihe ndị ọzọ egosila na enwere ike iji HULC na-ekesa na ndị ọrịa HCC dị ka akara nyocha n'ihi na lncRNA a na-edozi nke ukwuu na ndị ọrịa HCC ma e jiri ya tụnyere ndị nwere ahụike.71,86 N'ime lnRNA ndị ọzọ, a na-ahụta LINC00152 dị ka nchọpụta nchọpụta kachasị mma n'ihi AUC dị elu, nghọta na nkọwapụta ya.86 N'otu nnyocha, ngosipụta ọbara nke LINC00152 ji nwayọọ nwayọọ mụbaa site na njikwa ahụike nkịtị nye ndị ọrịa nwere CHB na cirrhosis, n'ikpeazụkwa bụ nke kachasị elu na HCC.Nnyocha nke okwu nke cirSMARCA5 na plasma nke ndị ọrịa nwere HCC egosila mbelata okwu na-aga n'ihu na HCC sitere na ịba ọcha n'anya ruo cirrhosis na ọnya precancerous.87 Nyocha nke usoro ROC kwadoro ikike nke circRNA ndị a na-amata ndị ọrịa nwere ịba ọcha n'anya ma ọ bụ imeju imeju na ndị nwere HCC, karịsịa ndị nwere ọkwa AFP n'okpuru 200 ng/mL.Na mgbakwunye, Zhu nyochara 13,617 cyclic RNA na plasma sample sitere na ndị ọrịa HCC metụtara HBV wee gosi na 6 cyclic RNA dị iche iche na HCC na HBV cirrhosis metụtara, na-atụ aro na cRNA nwere ike ịba uru.ihe nrịbama maka nyocha mmalite nke ndị otu dị ize ndụ dị ka ndị metụtara ọrịa imeju, ndị ọrịa sclerosis.88
Exosomes bụ akpụkpọ anụ vesicles 40-160 nm na dayameta;Ọtụtụ vesicles intracellular na-ejikọta akpụkpọ ahụ sel ma na-ahapụ ya n'ime matrix extracellular.Ha nwere ọtụtụ ihe na-arụ ọrụ, gụnyere lipids, proteins, RNA na DNA, ma na-ekere òkè dị mkpa na nzikọrịta ozi n'etiti sel, ma HCC na sel ndị na-abụghị HCC.89,90 Exosomes na-achịkwa ọganihu nke HCC site n'ịgbalite hepatocyte fibroblasts na sel stelate, mkpụrụ ndụ na-alụso ọrịa ọgụ, hepatocytes nkịtị, na sel HCC.91 Na microenvironment tumor, mkpụrụ ndụ tumor na-emepụta ọnụ ọgụgụ dị ukwuu nke exosomes nke a na-ebuga site na mkpụrụ ndụ cancer gaa na mkpụrụ ndụ akabeghị aka, nke na-etinye aka na oncogenesis, mmebi, na akara ngosi cellular.Nnyocha 92 egosila na exosomes nwere ike ịnyefe oncogenes na sel nkịtị n'oge usoro pathological, nke nwere ike ịbụ otu n'ime usoro nke mbuso agha tumo na metastasis.93 Ọrụ nke exosomes na ọganihu cancer nwere ike ịdị ike na kpọmkwem maka ụdị ọrịa cancer, 89 Exosomes nwere ike ịbanye n'ime ya site na mkpụrụ ndụ dị n'akụkụ ma ọ bụ dị anya iji dozie ọtụtụ mkpụrụ ndụ ihe nketa na mkpụrụ ndụ nnata nke nwere ike itinye aka na ions nkwurịta okwu intercellular na mmekọrịta microenvironment cellular, ha nwere ike. na-emeziwanye usoro metabolic na sel sel.94 Njirimara na mgbanwe dị ike nke mkpụrụ ndụ ihe nketa exosome na-egosipụta kpọmkwem njirimara na mgbanwe dị ike nke mkpụrụ ndụ tumor nne na nna, 95 nke bụkwa ihe ndabere maka iji exosomes na nchọpụta na prognosis nke ọrịa cancer, nakwa maka ịkọ nzaghachi onye ọ bụla na ọgwụgwọ anticancer. ..96
Ụzọ ụlọ nyocha ọdịnala maka ikewapụ na nyochaa exosomes dị mgbagwoju anya, ọtụtụ nzọụkwụ na-ewe oge, gụnyere ultracentrifugation, filtration, size chromatography, immunoaffinity purification, Western blotting, enzyme-linked immunosorbent assay (ELISA), PCR, and flow analysis.A na-emepụta sistemụ miniaturized na ụlọ nyocha-na-a-chip site na iji micro/nanotechnology maka ngwa ngwa, dị mma n'ọnọdụ ikewapụ exosomes.Nyocha nyocha nke Nanoparticle (NTA) bụ usoro a na-ejikarị eme ihe maka ịkọwa nha na ntinye nke exosomes, gụnyere ụzọ dị ka magnetik nanoparticles na polyhydroxyalkanoates.Ụzọ Microfluidic na electrochemical nwekwara ike ịchọpụta ngwa ngwa exosomes na nnukwu mkpụrụ.
Protein Exosomal bụ ihe nrịbama dị mkpa maka nchoputa nke HCC.N'ime ọmụmụ Arbelaiz, ọkwa nke 98 RasGAP SH3 protein binding (G3BP) na polymeric immunoglobulin receptor (PIGR) buliri elu nke ukwuu na exosomes sitere na HCC, na ntinye ntinye nke protein abụọ ahụ dị elu karịa nke AFP.Nbufe ígwè bụ ihe dị mkpa na-enye aka na mmepe nke HCC.Tseng kọrọ na hepcidin nwere ike ịrụ ọrụ dị mkpa na iguzogide HCC.99 Exosomes ewepụtara site na sera nke ndị ọrịa HCC nwere ọnụọgụ dị elu nke hepcidin mRNA dị iche iche karịa ndị ibe ha nwere ahụike, na-atụ aro na hepcidin nwere ike bụrụ ihe nyocha ọhụụ maka HCC.Protein 14-3-3ζ dị na exosomes nke 100 HCC na-emepụta nwere ike ibelata ọrụ cell T cell, mmụba, na ọdịiche dị iche iche ma nwee ike ime ka T cell gbanwee n'ime sel T na-achịkwa, na-ebute nkwụsị T cell.101 A na-akwado nke a site n'ọtụtụ ọmụmụ na-enyocha mgbapụ tumor site na onyunyo mgbochi ọrịa, 102 nke nwere ike inye aka na HCC tumorigenesis.
Na mgbakwunye na ọnụnọ ecRNA na plasma ma ọ bụ serum, enwere ike iji exosomes nwere RNA mee ihe maka nhazi oge na-adịghị ahụ anya na nyocha ụbụrụ mbụ na iji chọpụta mmalite mmalite na nzaghachi ọgwụgwọ.Ọkwa nke exosomal miRNA-21 na ọbara ọbara n'ime otu HCC dị okpukpu 2.21 karịa na otu CHB, na n'ime otu HCC ọ dị okpukpu 5.57 karịa na ndị nwere ahụike.Na nyocha Wang, exosomes mụbara HCC nke ukwuu ma e jiri ya tụnyere ndị ọrịa cirrhotic nwere ụkpụrụ AUC nke 0.83 (95% CI 0.74-0.93) na 0.94 (95% CI 0.88-1.00).104 Ihe data enwetara kọwapụtara itinye aka nke ụmụ irighiri ihe dị iche iche exosomal na nhazi nke oncogenesis na ọganihu HCC.105 Okwu serum nke miR-221, miR-103, miR-181c, miR-181a, miR-93 na miR-26a na-agbanwe agbanwe.na metastasis, na ọkwa miR21 dị elu karịa na ndị ọrịa HCC karịa na njikwa ahụike yana kwa na ndị ọrịa CHB.102 LncRNA nwere uru nchoputa na HCC.Nnyocha egosiwo na exosomes sitere na sera nke ndị ọrịa HCC nwere ọkwa dị elu nke LINC00161, LINC000635, na lncRNA na-arụ ọrụ site n'ịgbanwe ihe na-eto eto-β karịa ndị ọrịa na-enweghị HCC, na lncRNA ndị a na-ejikọta ya na ọkwa TNM na ụbụrụ ụbụrụ.110 Conigliaro et al.Achọpụtara CD90+ exosomes iji gosipụta ọkwa dị elu nke lncRNAH19, bụ nke mụbara ntọhapụ vaskụla endothelial uto (VEGF) na mmepụta VEGF-R1, si otú ahụ na-akpali angiogenesis.93 CircRNA bụ ụdị ncRNA exosomal ọzọ - egosipụtara na ọkwa dị ala mana kwụsiri ike n'ofe ụdị, circRNA na-egosipụtakwa nkọwapụta maka ụdị cell, ụdị anụ ahụ, ogbo mmepe, na ọrụ nhazi.111 circRNA bụ ihe nrịbama biomarkers maka ọrịa kansa n'oge na nke pere mpe.Nnwale ụlọọgwụ 112 na nso nso a egosila na nkọwapụta nke miRNA n'otu n'otu n'ịkọ HCC adịghị mma.Ya mere, nchọpụta mgbagwoju anya site na iji ọtụtụ nyocha (dịka, miR-122 na miR-48a na AFP) nwere ike ime ka nchọpụta nke HCC n'oge na ọdịiche nke HCC na cirrhosis.100
Ndị ọrịa nwere CHB na imeju imeju bụ ndị otu nwere nnukwu ihe ize ndụ maka ịmalite HCC.Maka otu ndị nwere nnukwu ihe ize ndụ, ozugbo enwetara nzaghachi nje virus na-adịgide adịgide, a ga-emepụta atụmatụ nleba anya dị ọnụ ahịa dabere n'ihe ize ndụ HCC, na nyocha mmalite bụ isi ihe na-eme ka nyocha na ọgwụgwọ HCC dị elu site na oke ọnụ ahịa bara uru2. ..Usoro nyocha mmalite maka ọrịa kansa nwere ọtụtụ oke: emebebeghị ụzọ nyocha mbụ dị irè maka ọtụtụ ụdị ọrịa kansa, na nrubeisi na-adịkarị ala.Tụnyere usoro nyocha mmalite oge ochie, teknụzụ biopsy mmiri nwere uru doro anya: ịdị mfe nke nlere anya, nchọpụta panrac, mmụgharị ihe nlele dị mma na nzaghachi dị mma maka ụdị dị iche iche nke etuto ahụ.N'ịnyere uru nke usoro ejikọtara na biopsy mmiri, a na-anwaleghị ojiji ha na nyocha HCC mgbe niile.N'agbanyeghị ọganihu a na-enwe na nchọpụta ziri ezi n'ọkwa molekụla, biopsy mmiri na-efu ọnụ iji chọpụta HCC n'ime ndị ọrịa lekwasịrị anya, na-amachi iji ya eme ihe n'ọtụtụ ebe ma e jiri ya tụnyere usoro onyonyo kpọmkwem dị ka ultrasound na imaging resonance magnet.113,114 Otú ọ dị, nnyocha e mere n'oge gara aga gosiri na mmiri mmiri biopsy gosipụtara uru dị ukwuu n'ihe gbasara afọ ndụ ndị a na-agbanwe agbanwe (QALY).115 Uru nke biopsy mmiri mmiri na carcinoma mmalite nke afọ na nasopharynx egosikwara.116,117 Echiche dị ugbu a bụ na biopsy mmiri mmiri nwere ike ịkwado serum biomarkers na nyocha redio na nchọpụta na nyocha nke etuto ahụ.117 118
Dị ka akwụkwọ ndị dị ugbu a si kwuo, nkà na ụzụ biopsy mmiri egosila mmetụta dị elu nke ukwuu na nkọwapụta na nyocha mmalite nke ndị otu nwere nnukwu ihe ize ndụ maka ọrịa cancer imeju.N'agbanyeghị ụdị biopsy mmiri dị, ọ nwere ike ịmata ọdịiche dị n'etiti HCC na ndị nwere nnukwu ihe ize ndụ na-enweghị HCC, na-atụ aro mkpa ọ dị n'oge nyocha dị ka ndịiche dị n'etiti ndị nwere nnukwu ihe ize ndụ na ndị nwere ahụike pụtara ìhè.ctDNA nwere obere ndụ ọkara ma enwere ike iji ya chọpụta HCC, yabụ mgbanwe ọ bụla na cDNA enwetara etuto nwere ike inye ihe akaebe doro anya nke ọganihu etuto ahụ, ọkachasị maka obere etuto ahụ.Ọkwa dị elu nke ctDNA na-egosi mmepe na mgbasa nke ọrịa kansa ma bụrụ ihe ngosi mmalite nke ọganihu na nlọghachi azụ.Na mgbakwunye, dabere na nsonaazụ ctDNA, ndị ọrịa nwere ike nweta ọgwụgwọ n'otu n'otu na nleba anya.Saịtị methylation 119 akọwapụtara nwere ike ịbụ akara ka mma karịa AFP maka njirimara mmalite nke HCC na nodules cirrhotic.N'okwu ndị a na-emegharị emegharị nke HCC, ọkwa dị elu nke cDNA na-egosi mbuso agha microvascular na nlọghachi azụ azụ na metastasis.Mgbanwe na nọmba nnomi jikọtara ya na nlanarị nke ndị ọrịa nwere HCC.Enwere ike iche na nlebanya cDNA nwere ike itinye aka na ọgwụgwọ HCC n'ozuzu ya, na cDNA nwere ike bụrụ ihe ngosi dị irè nke mgbanwe ọgwụgwọ.Ihe nrịbama dabere na mmụkọ mkpụrụ ndụ ihe nketa dị na ctDNA ejirila ntuziaka ụlọọgwụ anabatara maka ịdị mma yana nyochaa nguzogide ọgwụ.Nnwale ctDNA nwere ike ịbụ ngwaọrụ biopsy mmiri kacha baa uru maka nyocha mbụ.Ndị CTC na-ekerekwa òkè dị mkpa na nyocha mmalite nke otu HCC nwere nnukwu ihe ize ndụ.Ihe nrịbama dị iche iche nke CTC metụtara HCC dị mkpa na mmalite, mmepe, na nlọghachi nke HCC.Dị ka akpụkpọ anụ vesicles, exosomes na-etinye aka na nkwukọrịta intercellular, karịsịa na sel HCC.MicroRNA na-ekesa kwụsiri ike n'ọbara, yabụ nwere ike ịba uru karịa nyocha mbụ nke HCC.Nke nta nke nta, achọpụtara protein exosomal na exosomes bara ụba nke RNA, na amụma amụma ha nwere maka HCC kwadoro.N'ụzọ na-akpali mmasị, etiologies dị iche iche nke HCC nwekwara ike jikọta ya na mmụgharị dị iche iche, yabụ anyị nwere ike họrọ ụdị biomarkers dị iche iche maka nyocha oge mbụ dabere na etiologies dị iche iche nke HCC.120
Otú ọ dị, usoro biopsy mmiri dị ugbu a bụ ihe a na-enyo enyo n'ihe gbasara nkwụsi ike na enweghị ike ịme nyocha mbụ ma ọ bụ nlekota nke HCC, mana ọ ka nwere ike ịkwado nyocha na nyocha nke onye ọ bụla.121 Dị ka ụdị biopsy mmiri mmiri, nchọpụta na onyonyo nke ctDNA, CTC, cfRNA na exosome-Associated AFP ma ọ bụ PIVKA-II nwere ngwa na-ekwe nkwa na nchọpụta mmalite na prognosis nke HCC.Agbanyeghị, usoro ntọhapụ ctDNA n'ime ọbara ka ka ga-akọwapụta ya.Ikpughe njirimara ndu ndu nke ctDNA nwere ike ime ka ojiji ya dị ka akara.Obere ctDNA dị na mgbasa ozi na njikwa ihe nlele siri ike bụ ihe ịma aka maka mmejuputa ụlọ ọgwụ nke nchọpụta cDNA na HCC.Na mgbakwunye, mmụgharị mkpụrụ ndụ ihe nketa enweghị njirimara akọwapụtara nke na-enye ohere njirimara ziri ezi nke carcinogens.Ebe ọ bụ na ọtụtụ mkpụrụ ndụ ihe nketa na somatic variants dịkwa na anụ ahụ nkịtị, mmụgharị mkpụrụ ndụ ihe nketa nke mmiri mmiri biopsy chọpụtara nwere ike ịbụ nke oke uru na nyocha mmalite maka HCC.122 Mgbochi nke ebumnuche mkpụrụ ndụ bara uru akọwapụtara nke ọma na ndị na-ahụ maka biomarkers na-enyere aka ịmata ọdịiche dị na cDNA na DNA na-abụghị tumor bụ ihe kacha mkpa n'iji cDNA eme ihe.enweghị uru nke nrịbama dị nro na nke akọwapụtara maka nchọpụta nke CTC.Naanị mkpụrụ ndụ ga-ekwe omume nwere ikike metastatic ka achọtara, yana ezigbo nchikota nke akara nrịbama CSC amabeghị.Mwepu nke CTC maka omenaala na nleba anya profaịlụ mgbanwe ha bụkwa ọrụ siri ike.N'ihi nsogbu dị na njirimara, ikewapụ na ịdị ọcha nke exosomes, usoro mkpụrụ ndụ a kapịrị ọnụ ka edoghị anya, na ọmụmụ ihe gara aga banyere usoro exosomes na HCC adịghị n'ime omimi, na ụzọ e si ahazi miRNA, lncRNA na protein n'ime exosomes. , ma o doghị anya ma iwere exosome bụ ụdị usoro a kapịrị ọnụ.Ojiji nke exosomes maka nchoputa na ọgwụgwọ nke HCC ka na-na preclinical ogbo.Enweghị ọkọlọtọ nke usoro biopsy mmiri mmiri, dị ka ụdị tubes eji achịkọta ọbara, oke ọbara, nchekwa nchekwa na nchọpụta, ikewapụ na ịba ụba, nwere ike igbochi iji ha eme ihe na-eme ihe na-eme ihe na-emekarị n'ụlọ ọgwụ n'ihi ọdịiche dị na omume n'ofe ụlọ ọgwụ.A ka ga-enyocha ịdị irè nke biopsy mmiri mmiri na nyocha mbụ, nyocha, nleba anya arụmọrụ, na amụma HCC, ọkachasị maka ndị otu nwere nnukwu ihe egwu.Teknụzụ biopsy mmiri nwere ikike dị ukwuu ma a na-atụ anya na a ga-eji ya mee ihe na usoro ọgwụgwọ ọrịa kansa imeju n'ọdịnihu dị nso.
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Oge nzipu: Sep-23-2022