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E hoʻopaʻa inoa me kāu kikoʻī kikoʻī a me ka lāʻau lapaʻau kikoʻī o ka hoihoi, a e hoʻohālikelike mākou i ka ʻike āu e hāʻawi ai me nā ʻatikala i loko o kā mākou waihona nui a leka uila iā ʻoe i kahi kope PDF koke.
ʻO Ding Jingnuo, Zhao Weifeng, Keʻena o nā maʻi maʻi maʻi, ka Halemai Hoʻohui Mua o Suzhou University, Suzhou City, Jiangsu Province, 215000 Tel.nā maʻi koko o ka ʻōnaehana digestive me ke ola holoʻokoʻa o 5 mau makahiki he 14.1%.Nui nā poʻe maʻi me ka HCC i ʻike ʻia ma kahi pae kiʻekiʻe, no laila pono ka nānā mua ʻana e hōʻemi i ka make mai ka HCC.Ma waho aʻe o nā hōʻailona ʻike maʻamau e like me ka serum alpha-fetoprotein (AFP), lens lectin-reactive alpha-fetoprotein (AFP-L3), a me ka prothrombin abnormal (vitamin K deficiency-induced protein II, PIVKA-II), nā ʻenehana biopsy wai. Ua hōʻike ʻia he waiwai diagnostic i ka ʻike ʻana i ka HCC.Ke hoʻohālikelike ʻia i nā kaʻina hana invasive, hiki i ka wai biopsy ke ʻike i ke kahe ʻana o nā metabolites malignant.ʻIke ʻia nā ʻenehana biopsy wai i ka puni ʻana o nā cell tumo, ka puni ʻana i ka DNA tumo, RNA kaʻapuni, a me nā exosome a hoʻohana ʻia no ka nānā mua ʻana, ka hōʻoia, a me ka loiloi prognostic o HCC.Hōʻike kēia ʻatikala i ka molecular biology a me ka hoʻohana ʻana i nā ʻano hana biopsy wai e hoʻokaʻawale i nā biomarkers hoʻohiki i hiki ke koho ʻia no ka loiloi mua ʻana o ka HCC e hoʻomaikaʻi i ka nānā mua ʻana o nā pūʻulu HCC kiʻekiʻe.Hua'ōlelo: wai biopsy technique, hepatocellular carcinoma, high-risk group.
ʻO ka maʻi maʻi hepatocellular (HCC) he maʻi maʻi maʻamau maʻamau o ka ʻōpala digestive, ka helu ʻeono i waena o nā hihia hou o nā maʻi ʻino ma nā kāne a me nā wahine.1 Ma ke ao holoʻokoʻa, ʻo ka maʻi ʻaʻai ʻaʻai ke kolu o ke kumu nui o ka make ʻana o ka maʻi kanesa ma hope o ka maʻi kanesa a me ka maʻi ʻaʻai kala, ʻo ia ka 8.3% o nā make pili i ka maʻi kanesa mai nā neoplasms malignant.1 Ua pili pili ka prognosis o HCC i ke kahua ma ka maʻi.ʻO nā kumu nui o ke ola maikaʻi ʻole i ka HCC ʻo ia nā metastases intrahepatic, portal venous tumor thrombi, a me nā metastases mamao e pale ana i ka wehe ʻana, a ʻo ka nui o kēia mau ʻano i loaʻa i nā maʻi i ka manawa o ka maʻi.
Ma muli o nā alakaʻi diagnostic a me ka mālama ʻana, ʻo nā kumu pilikia nui no ka hoʻomohala ʻana i ka HCC ʻo ia ka cirrhosis o ke ake, ka maʻi hepatitis B mau loa (HBV) a i ʻole ka maʻi hepatitis C (HCV), ka maʻi ʻawaʻawa momona momona, a me ka maʻi momona momona ʻole (NAFLD). ).2 Eia kekahi, ʻo nā kumu pilikia no ka HCC, ʻo ia ka ʻai ʻana i ka meaʻai aflatoxin-contaminated, schistosomiasis, nā kumu ʻē aʻe o ka cirrhosis, kahi moʻolelo ʻohana o ka maʻi maʻi ate, ka maʻi diabetes, ka momona, ka puhi ʻana, a me ka hōʻeha ʻana i ka ate.Pono nā hui koʻikoʻi koʻikoʻi he 35 a me 45 mau makahiki e nānā mau i ka lāʻau lapaʻau.ʻO ka nānā mua ʻana he hoʻolālā lapaʻau koʻikoʻi nui e hoʻomaikaʻi i ke ola holoʻokoʻa o nā maʻi me HCC.
Paipai ʻia nā biomarkers e like me AFP, AFP-L3 a me PIVKA-II no ka nānā mua ʻana o HCC3,4.Ua hōʻike nā ʻenehana biopsy wai i nā hopena hoʻohiki i ka hoʻomaʻamaʻa mua ʻana a me ka loiloi lapaʻau.5,6 Ua loaʻa ka holomua nui i ka biopsy wai wai HCC, hiki ke loaʻa ka ʻike a me ka kikoʻī ma mua o nā mea hoʻohana maʻamau e like me AFP (Table 1).
ʻO AFP kahi biomarker i hoʻohana nui ʻia ma HCC a ʻo ia ka biomarker kikoʻī loa i hoʻohana nui ʻia no ka nānā mua ʻana, ka maʻi ʻana, a me ka loiloi o ka maʻi.ʻO ka pae kiʻekiʻe o ka AFP i manaʻo ʻia he kumu pilikia no ka holomua o ka HCC.7,8 Ke piʻi nei ka nui o ka ʻike ʻana o ka maʻi hepatocellular carcinoma liʻiliʻi (sHCC) me ka hoʻomohala ʻana o ka ultrasound a me ka helu helu helu, a ua ʻike ʻia ʻo AFP i ka ʻike ʻole i ka ʻike ʻana o ka hHCC i ka hana lapaʻau.Wahi a kahi noiʻi multicentre retrospective9, loaʻa ka maikaʻi o AFP ma 46% (616/1338) o nā hihia HCC a me 23.4% (150/641) o nā hihia sHCC.Eia kekahi, ua hoʻokiʻekiʻe ʻia nā pae AFP i nā poʻe maʻi me ka maʻi ate a me ka cirrhosis.10 No laila, loaʻa i ka AFP kahi hopena screening palena no ka sHCC.11 Wahi a ka Asia-Pacific Clinical Practice Guidelines for Hepatocellular Carcinoma, ʻaʻole ʻōlelo ʻia ka hoʻohana ʻana i ka AFP. he waiwai diagnostic kiʻekiʻe ma HCC.13 Ke hoʻohālikelike ʻia me ka biopsy kiko, ʻike mua ka biopsy wai i nā metabolites pili i ka maʻi maʻi i loko o nā wai kino (ke koko, saliva, ka wai pleural, ka wai cerebrospinal, a i ʻole ka mimi) a ʻoi aku ka liʻiliʻi o ka invasive i nā ʻiʻo.14 Eia kekahi, hiki i nā biopsies wai ke hōʻike i nā hiʻohiʻona ʻino ʻaʻole i loaʻa i loko o ka ʻiʻo tumo mua.15 ʻAʻole i hoʻāʻo ʻia nā biopsies wai i ka hoʻomaʻamaʻa lapaʻau no nā ʻano maʻi ʻokoʻa a pau, akā ʻo ko lākou hiki ke hōʻoia i ka maʻi kanesa ke huki nei i ka manaʻo o nā oncologists.16 Hiki i ka wai biopsy ke ʻike i ke kaʻapuni ʻana i nā sela tumo (CTCs), ka DNA tumora (cDNA), ka RNA manuahi (ecRNA), a me nā exosome.Ma kēia ʻatikala, e kūkākūkā mākou i nā ʻano, kuleana, a me ka hoʻohana ʻana i nā ʻano hana biopsy wai i ka nānā mua ʻana o nā pūʻulu HCC kiʻekiʻe.
Ua wehewehe mua ʻia ka DNA extracellular (cfDNA) i nā laʻana koko mai nā kānaka olakino ma 1948 e Mandel et al.ʻO 17 cfDNA he ʻāpana DNA manuahi ʻole ma kahi o 160-180 bp ka lōʻihi, mai nā lymphocytes a me nā cell myeloid.ʻO ka ctDNA kahi ʻāpana DNA mutant kikoʻī i hoʻokuʻu ʻia e nā cell tumor i loko o ke koko peripheral, e hōʻike ana i ka ʻike genomic o nā cell tumor ma hope o kekahi mau kaʻina pathophysiological, me ka necrosis, apoptosis, a me ka excretion.ʻOkoʻa ākea ka hapa o ka ctDNA i ka cfDNA a pau me ke ʻano tumo, a ua hōʻike ʻia nā ʻāpana cDNA ma lalo o 167 bp ka lōʻihi.18 Ua hōʻike ʻia ka haʻawina a Underhill he ʻoi aku ka pōkole o nā ʻāpana cfDNA ma mua o ka cfDNA maʻamau.ʻO ka hoʻonui ʻana i kekahi mau ʻāpana o ka lōʻihi o ka ʻāpana cfDNA hiki ke hoʻomaikaʻi i ka ʻike ʻana o ka cDNA e pili ana me nā maʻi maʻi non-metastatic solid.Ua hōʻike nā haʻawina e loaʻa ana ka ctDNA ma luna o 75% o ka pancreatic holomua, colon, bladder, gastrointestinal, ate, ovarian, breast, melanoma, a me nā maʻi maʻi poʻo a me ka ʻāʻī.20,21 Eia naʻe, ʻo ka nui o ka ctDNA i loko o ke koko e pili ana i ka wahi o ka ʻōpū.22 Ma kahi noiʻi a Bettegoud, ua ʻike ʻia nā maʻi me nā maʻi maʻi colorectal, umauma, ate, akemāmā, a me ka prostate i nā pae kiʻekiʻe o ka cDNA i ko lākou koko ma mua o nā maʻi maʻi ʻē aʻe.I ka hoʻohālikelike ʻana, i nā poʻe maʻi me ka maʻi maʻi waha, ka maʻi maʻi pancreatic, ka maʻi maʻi ʻōpū, a me ka glioma, ʻoi aku ka haʻahaʻa o ka cDNA i ke koko.iwakāluakumakahi
No ka mea, aia ka ctDNA i nā hoʻololi genetic like e like me nā cell tumor mua, hiki ke hoʻohana ʻia ka cDNA no ka ʻike ʻana i nā mutations kikoʻī kikoʻī heterogeneous a me nā loli epigenetic, me ka methylation, hydroxymethylation, nā ʻano nucleotide hoʻokahi, a me nā ʻano helu kope.iwakāluakūmākolu
ʻO ka methylation DNA kekahi o nā hoʻololi epigenetic maʻamau i hopena i ka hoʻopaʻa ʻana i ke ʻano.Ke hoʻohālikelike ʻia me nā cell maʻamau, aia nā ʻokoʻa i ka pae holoʻokoʻa o ka methylation o ka genome cell tumo, ʻoi aku ka nui o ka methylation o nā genes suppressor tumor, hiki ke ʻike ʻia i ka wā mua, e hōʻike ana i nā loli i ka methylation DNA he hōʻailona o ka wā mua. ʻike ʻana i ka tumorigenesis.Hiki ke hoʻopau ʻia nā genes suppressor tumor e pili ana i ka HCC e ka methylation promoter, a laila e hoʻoulu ai i ka tumorigenesis.ʻO 24 DNA methylation kahi hōʻailona kūpono no ka ʻike mua ʻana o nā maʻi maʻi ma muli o kona kiko kikoʻī, ʻike ʻia, a me ke kūʻokoʻa makahiki.Eia kekahi, ʻoi aku ka maʻamau o ka methylation DNA i ka hoʻohālikelike ʻana i nā hoʻololi somatic no ka mea ʻoi aku ka nui o nā wahi i hoʻopaʻa ʻia a me nā wahi CpG i hoʻololi ʻia i kēlā me kēia wahi o ka genome i hoʻopaʻa ʻia.25 Ma waho aʻe o nā pūnaewele CpG he nui, ua ʻike ʻia kahi helu nui o nā loci hypermethylated kūʻokoʻa ma ctDNA ma DBX2, THY1, MT1M, INK4A, VIM, FBLN1, a me RGS10.26 Xu et al.ʻO ka hoʻohālikelike ʻana i nā laʻana cfDNA mai 1098 mau maʻi HCC a me 835 mau mana olakino he mau genes pili me HCC i ʻike ʻia e pili ikaika me nā pūlima cDNA methylation plasma pili.25 Ma muli o ka nānā ʻana o ke keʻena hoʻokolohua, ua hoʻomohala ʻia kahi hiʻohiʻona wānana i loaʻa nā māka methylation 10 me ka naʻau a me ka kikoʻī o 85.7% a me 94.3%, kēlā me kēia, a ua hoʻopili nui ʻia kēia mau hōʻailona me ka nui o ka tumo, ka pae tumo, a me ka pane i ka mālama ʻana.Hōʻike kēia mau hopena i ka hoʻohana ʻana i nā māka methylation cDNA e paʻa i ka ʻōlelo hoʻohiki nui i ka maʻi maʻi, ka nānā ʻana, a me ka wānana o HCC.I loko o kahi kŘkohu methylation me ekolu mau genes aberrantly methylated (APC, COX2, RASSF1A) a me hoʻokahi miRNA (miR203) i hōʻike ʻia e Lu et al27, ua hoʻohālikelike ʻia ka naʻau a me ka kikoʻī o ke kumu hoʻohālike 27 no ka ʻike ʻana i ka HCC pili i ka HBV.80%.Eia kekahi, hiki i ke kumu hoʻohālike ke ʻike i ka 75% o nā maʻi HCC undiagnosed me kahi pae AFP o 20 ng/mL.ʻO ka gene no ka ʻohana Ras-associated domain family 1A protein (RASSF1A) ʻo ia ke kaʻina DNA repetitive nui i ka genome kanaka.Araujo et al.Ua hoʻoholo ʻo hypermethylation o ka mea hoʻolaha RASSF1A hiki ke lilo i biomarker waiwai no ka nānā mua ʻana o ka HCC a me kahi pahuhopu molekala no ka epigenetic therapy.28 Ma kahi noiʻi, ua loaʻa ka serum RASSF1A promoter hypermethylation ma 73.3% o nā maʻi me HCC.29 ʻElemu nucleotide long interspersed 1 (LINE-1) ʻo ia kekahi mea hoʻolaha hoʻololi hou.Ua loaʻa ka Hypomethylation o LINE-1 i ka DNA o 66.7% o ka HCC serum samples a ua pili pū me ka hoʻi hou ʻana a me ke ola maikaʻi ʻole ma hope o ka wehe ʻana.29 ʻO ka Hypermethylation kahi hana maʻamau maʻamau e pāʻani i kahi kūlana kūʻokoʻa i ka hoʻomohala ʻana o ka ate cirrhosis a me ka HCC.30 I ka hoʻokaʻawale ʻana, ʻo ka hydroxymethylation kahi kaʻina demethylation e hoʻoulu ai i ka hoʻoulu hou ʻana a me ka hōʻike ʻana, a hiki ke hoʻohana ʻia ka ʻike ʻana o ka huahana 5-hydroxymethylcytosine (5-hmC) i kēia kaʻina e ʻike ai i kahi ʻōpū.Hoʻopili ʻia ka methylation a me ka hydroxymethylation o cDNA me ka tumorigenesis a hiki ke kōkua i ka nānā mua ʻana o ka HCC.Ma kahi noiʻi o 2554 mau kumuhana, 31 genome-ākea 5-hmCs i loaʻa i loko o cfDNA samples, a me 32 genes i ikeia ma ka hoohalike ana i 5-hmC sequences i HCC maʻi a me kiʻekiʻe-pilikia pūʻulu e like me ka mau maʻi maʻi.Nā hiʻohiʻona diagnostic o nā maʻi ate.a me ka cirrhosis.ʻOi aku ka maikaʻi o kēia kükohu ma mua o AFP i ka hoʻokaʻawale ʻana i ka HCC mai ka ʻiʻo non-tumor.
Hiki i nā hoʻololi ʻana i nā ʻāpana coding ke alakaʻi i nā mea ʻino transcriptional, hiki ke alakaʻi i nā loli i nā kaʻina protein a me ka maʻi kanesa.He mau hōʻailona genomic koʻikoʻi nā ʻano ʻano nucleotide hoʻokahi no ka nānā ʻana i ka maʻi maʻi ma muli o ko lākou hilinaʻi kiʻekiʻe a me ke kiko kiʻekiʻe a me ka kiko kiko.Nui nā haʻawina e pili ana i ka HCC me ka hoʻohana ʻana i ka hanauna e hiki mai ana (NGS) no ka exome a me ka genome sequencing holoʻokoʻa o ka maʻi kanesa ua ʻike i nā genes cellular mutated maʻamau e like me TP53 a me CTNNB1, a me kekahi pū kekahi me ARID1A, MLL, IRF2.ʻO nā genes hou, ATM, CDKN2A, FGF19, PIK3CA, RPS6KA3 a me JAK1 e hōʻike ana i nā helu hoʻololi haʻahaʻa. Hōʻike ka loiloi hana mutant gene i ka hoʻololi ʻana i ka chromatin remodeling, Wnt / β-catenin a me JAK / STAT ka hoʻololi ʻana i ka hōʻailona, ​​ke ala pōʻai P53-cell, nā mea hoʻololi epigenetic, nā ala koʻikoʻi oxidative, ke ala PI3K / AKT / MTOR a me ka RAS / RAF / MAPK kinase ala pāʻani koʻikoʻi koʻikoʻi i ka HCC oncogenesis.32,33 Ma kahi noiʻi kahi i ʻike ʻia ai nā hoʻololi pili i ka tumo, ua ʻike ʻo Huang et al ʻo ke alapine o nā hoʻololi pili i ka maʻi maʻi e pili ana i ka ctDNA ʻo 19.5%, a ʻo 90% ka kikoʻī. .34 Eia kekahi, ʻoi aku ka nui o nā maʻi i loaʻa i ka hoʻouka ʻana i ka vascular invasion (P=0.041) a me ke ola hou ʻole ʻana (P<0.001). Hōʻike ka loiloi hana mutant gene i ka hoʻololi ʻana i ka chromatin remodeling, Wnt / β-catenin a me JAK / STAT ka hoʻololi ʻana i ka hōʻailona, ​​ke ala pōʻai P53-cell, nā mea hoʻololi epigenetic, nā ala koʻikoʻi oxidative, ke ala PI3K / AKT / MTOR a me ka RAS / RAF / MAPK kinase ala pāʻani koʻikoʻi koʻikoʻi i ka HCC oncogenesis.32,33 Ma kahi noiʻi kahi i ʻike ʻia ai nā hoʻololi pili i ka tumo, ua ʻike ʻo Huang et al ʻo ke alapine o nā hoʻololi pili i ka maʻi maʻi e pili ana i ka ctDNA ʻo 19.5%, a ʻo 90% ka kikoʻī. .34 Eia kekahi, ʻoi aku ka nui o nā maʻi i loaʻa i ka hoʻouka ʻana i ka vascular invasion (P=0.041) a me ke ola hou ʻole ʻana (P<0.001).Hōʻike ka loiloi hana mutant gene i ka hoʻololi ʻana i ka chromatin remodeling, Wnt/β-catenin a me JAK/STAT hōʻailona, ​​P53 cell cycle alahele, epigenetic modifiers, oxidative stress pathways, PI3K/AKT/MTOR alahele, a me RAS/RAF/MAPK ala kinase. he kuleana koʻikoʻi i ka HCC tumorigenesis.32,33 Ma kahi noiʻi i loaʻa nā hoʻololi pili i ka maʻi, Huang et al.Ua ʻike ʻia ʻo ka pinepine o ka ctDNA-dependent tumor-associated mutations he 19.5% a ʻo ka kikoʻī he 90%..34 Кроме того, у пациентов с сосудистой инвазией чаще встречались мутации цДНК (P=0,041) и болызией чаще встречались мутации цДНК (P=0,041) и болызка1 более кодиция (P=0,041). .34 Eia kekahi, ʻoi aku ka nui o nā hoʻololi cDNA (P=0.041) i nā poʻe maʻi me ka invasion vascular a me ke ola pōkole ʻole o ka maʻi (P<0.001).Hōʻike ka loiloi hana o nā genes mutant i ka chromatin remodeling, Wnt / β-catenin a me JAK / STAT hōʻailona, ​​​​ke ala P53 cell cycle, nā mea hoʻololi epigenetic, ke ala koʻikoʻi oxidative, ke ala PI3K / AKT / MTOR, a me ka RAS / RAF / MAPK He kuleana koʻikoʻi ke ala kinase i ka oncogenesis o HCC. 323ʻAʻole 一项项检测到 Na Mele Aloha, 频率 为 18, 可能 更侵犯) 患者 5 更侵犯 Ctdna突变（P=0.041）和更短的无复发生存期（P<0.001）。 32.33 一 一项检测检测: 研究 研究研究 研究研究 研究, 为 为 更发生 更发生 "和更" 和为为111) 和和短的无复发生存期（P<0.001）。32,33 I loko o kahi noiʻi i loaʻa i nā ʻano hoʻololi pili i ka maʻi tumora, Huang et al.ua ʻike ʻia he 19.5% ka hoʻololi ʻana i pili i ka maʻi maʻi i ka cDNA me kahi kikoʻī o 90% 34. Eia kekahi, ʻoi aku ka nui o nā maʻi i loaʻa i ka hoʻoulu ʻana i ka cDNA.мутация (P = 0,041) и более короткая безрецидивная выживаемость (P <0,001). ka hoʻololi ʻana (P=0.041) a me ke ola pōkole ʻole o ka maʻi (P<0.001).ʻO TP53 kekahi ʻano mea hoʻokele HCC maʻamau, nona ka nui o ka mutation ma luna o 30%.Ua hōʻike ʻia nā haʻawina ʻo ka pinepine o ka hoʻololi ʻana o TP53 i ka ctDNA i ke koko a me ka mimi mai 5% a 60%.35 Ua hōʻike ʻia ka haʻawina a Johan e like me ka ctDNA mutation spectrum ma hope o ka HCC me ka HCC mua, me ka mea hoʻolaha TERT (51%), TP53 (32%), CTNNB1 (17%), PTEN (8%), nā hoʻololi i loko. AXIN1 ., ARID2, KMT2D a me TSC2 (6% kēlā me kēia).36 He kuleana koʻikoʻi ka β-catenin (CTNNB1) oncogene i ke ala hōʻailona Wnt.Hiki i ka transcription coactivator CTNNB1 ke hoʻoikaika i ka hōʻike gene, hiki ke alakaʻi i ka hoʻonui ʻana o ka cell, inhibition o apoptosis, a me angiogenesis.Hiki i ka CTNNB1 ke launa pū me TERT e hoʻohuli i ka hoʻololi hepatocyte.33 Hoʻololi pinepine ʻia ka mea hoʻolaha TERT i kekahi mau maʻi koko paʻa.ʻO ka hoʻololi ʻana ma TERT, kekahi o nā hoʻololi genetic mua loa i ka hoʻololi ʻino ʻana o ka HCC, hiki ke alakaʻi i ka telomerase reactivation i loko o nā hepatocytes cirrhotic a hiki ke hāpai i ka hoʻonui ʻana a pale i ka ʻelemakule.Ua hōʻike ʻia nā hoʻololi ʻana i ka mea hoʻolaha TERT 33-37 i ka 59-90% o nā maʻi me nā nodules ate proliferative a me ka HCC mua a pili pū me ke ola.38
ʻO nā hoʻololi helu kope (CNA) he ʻano subtype koʻikoʻi o nā hoʻololi somatic.Ua hōʻike ʻia ka noiʻi ʻana ʻo ka palahalaha nui a me ke kaumaha o CNA he pūlima genomic hiki ke wānana i ka infiltration immune a me ka haʻalele ʻana i kekahi mau ʻano maʻi kanesa.39 ʻO ka hōʻailona infiltration ikaika, ka hana cytolytic kiʻekiʻe, ka mumū nui a me nā hōʻailona genetic pili me ka hōʻike antigen ma HCC.ʻO ka nānā ʻana i ka ʻikepili o nā polymorphism nucleotide hoʻokahi i nā kumuhana 477 i hōʻike i kahi haʻahaʻa haʻahaʻa ma ka CNS.ʻO ka hoʻohālikelike ʻana, ʻo nā maʻi maʻi chromosomal unstable me kahi ukana CNA kiʻekiʻe e hōʻike ana i nā hōʻailona o ka hōʻole ʻana a pili pū me ka proliferation, DNA repair, a me TP53 dysfunction.Xu et al.ua hōʻike i ka hui HCC i nā helu CNA kiʻekiʻe ma mua o ka hui maʻi ate maʻi.40 Me ka hoʻohana ʻana i ka hoʻokaʻina genome holoʻokoʻa o kahi cell hoʻokahi, ua ʻike ʻia nā CNA e ʻike mua ʻia i ka hepatocarcinogenesis a paʻa mau i ka wā o ka piʻi ʻana o ka tumo.41 ʻO Chung et al.Ua ʻike ʻia ua hoʻokiʻekiʻe nui ʻia nā pae cfDNA i nā maʻi HCC a ʻo ka genome-ākea CNA i cfDNA he hōʻailona kūʻokoʻa kūʻokoʻa koʻikoʻi i nā maʻi HCC i mālama ʻia me ka sorafenib.42 ʻO ka poʻe maʻi me ke kaumaha CNA kiʻekiʻe aʻe e loaʻa i ka maʻi a me ka make ma mua o ka poʻe me ka haʻahaʻa CNA haʻahaʻa.Ollerich et al.ʻike ʻia hiki ke hoʻohana ʻia ka helu helu instability index (CNI) e loiloi i ka CNA i ka cfDNA o nā maʻi maʻi maʻi.Ua ʻike lākou ua ʻoi aku ka nui o nā helu CNI ma mua o kahi pūʻulu mana, e loiloi ana i ka pane ʻana o ka maʻi i ka chemotherapy systemic a me ka immunotherapy.43 Hōʻike kēia mau hopena i nā CNA i loaʻa i nā specimen biopsy wai hiki ke lilo i mau hōʻailona prognostic i nā poʻe maʻi me ka maʻi kanesa kiʻekiʻe.HCC ma ke kua o ka systemic therapy.
I kēia manawa, hiki ke hoʻokaʻawale ʻia nā ala i hoʻohana ʻia no ka ʻike ʻana i ka ctDNA i nā ʻano i hoʻopaʻa ʻia a me nā ʻano hana ʻole.ʻO ka pōkole, ʻo nā ala i manaʻo ʻia e like me ka digital polymerase chain reaction (dPCR), BEAMing digital PCR, Amplification Refractory Mutation System-PCR, Capp-Seq a me Tam-Seq he maʻalahi loa i nā genes i koho mua ʻia.Hāʻawi nā ʻano hana ʻokoʻa e like me ka genome sequencing holoʻokoʻa a me NGS i kahi ʻike piha o ka ʻāina genomic holoʻokoʻa.44 Ke hoʻohālikelike ʻia me nā panela i hoʻopaʻa ʻia, hiki i ke kaʻina genome holoʻokoʻa ke ʻike ʻaʻole wale i nā hoʻololi ʻana a me nā hoʻokomo ʻana, akā i ka hoʻonohonoho hou ʻana a me nā ʻano helu kope.prognosis, a ʻo CTC a me cfDNA nā hōʻailona maikaʻi e hiki ke hoʻohana ʻia no ka nānā ʻana i ka HCC.45 Eia kekahi, ʻoi aku ka maikaʻi o ka loiloi cfDNA i ka ʻike ʻana iā HCC.ʻO Yan et al.hōʻike i ka cfDNA i loko o ka plasma o nā maʻi me ka HCC i ʻoi aku ka kiʻekiʻe ma mua o nā maʻi me ka fibrosis ate a me nā mana olakino.Hoʻohālikelike ʻia me AFP, manaʻo ʻia ʻo ctDNA e lilo i mea hōʻailona hōʻailona maikaʻi loa no ka HCC mua.46 Ma kahi noiʻi ʻana o 47 wai biopsies i hoʻāʻo i ka cfDNA a me ka protein i loko o ka heluna heluna kanaka, ua hōʻike ʻia lākou he kūpono i ka hoʻokaʻawale ʻana i nā maʻi me ka HCC mai nā maʻi me ka HCC ʻole.Ma ka hahai ʻana o 331 ultrasound maʻamau a me AFP-negative nā mea maʻi, ʻo ka sensitivity a me ka kikoʻī o cfDNA no ka hōʻoia ʻana i ka HCC he 100% a me 94%, no laila hiki i ka cDNA ke ʻike i ka HCC i nā poʻe asymptomatic HBsAg seropositive.Ma ka haʻawina Yeo48, loaʻa kahi alapine kiʻekiʻe (92.5%) o ka hypermethylation o ka mea hoʻolaha RASSF1A i nā maʻi me HCC.Eia kekahi, ʻo Xu et al.ua hana i kahi hiʻohiʻona diagnostic e wānana i ka HCC me ka hoʻohana ʻana i kahi panel o nā māka methylation kikoʻī me kahi kikoʻī a me ka naʻau o 90.5% a me 83.3%, kēlā me kēia.Hāʻawi ka papa i nā maʻi me ka HCC e hoʻokaʻawale ʻia mai nā maʻi me nā maʻi ʻē aʻe, ʻoi aku ka maikaʻi ma mua o AFP.Ua ʻike pū lākou ʻo nā mana maʻamau i hoʻāʻo maikaʻi ʻia he mau kumu pilikia no ka HCC, e like me ka maʻi HBV a i ʻole ka mōʻaukala o ka hoʻohana ʻana i ka waiʻona.25 Manaʻo mākou e hiki i nā mea koʻikoʻi koʻikoʻi no ka HCC ke hoʻoikaika i ka hypermethylation o cfDNA, a laila kōkua i ka holomua o ka HCC, a no laila hiki i ka cfDNA ke hana i kahi kuleana nui i ka nānā ʻana i nā hui kiʻekiʻe.Cai et al.hōʻuluʻulu i ka piha piha o nā mutations ctDNA a hāʻawi i kahi hoʻolālā ikaika no ka loiloi ʻana i ke kaumaha o ka maʻi maʻi.49 Hiki i kēia hoʻolālā ke hoʻomaopopo i ka tumorigenesis he median o 4.6 mahina ma mua o ka hoʻololi ʻana o ke kiʻi a ua hōʻike i ka hana diagnostic ʻoi aku ka maikaʻi ma mua o ka serum biomarkers AFP, AFP-L3, a me PIVKA-II.Ua hōʻike ʻia ka waiwai diagnostic o ka hoʻāʻo cDNA i ka wā ʻaʻole i loaʻa ka loiloi kiʻi, no laila he waiwai ka hoʻāʻo cDNA i ka hōʻoia ʻana o ka HCC mua i nā hui kiʻekiʻe.I kēia mau lā, ua hoʻohana nā kānaka ʻepekema i ka ʻenehana NGS no ka nānā ʻana i nā hōʻailona o ka hoʻololi genetic multivariate (me 5-hydroxymethylcytosine, 5′-motif, fragmentation, nucleosome trace, HIFI) ma 3204 clinical samples a me cfDNA.50 Ua hōʻoia hou ʻia nā hiʻohiʻona HIFI me ʻekolu kaʻaahi kūʻokoʻa, hoʻāʻo, a me nā hoʻonohonoho hoʻāʻo i hōʻike i ka hoʻokae paʻa a hilinaʻi ma waena o ka HCC a me ka heluna HCC ʻole me 95.79% a me 95.42% ʻike i ka HCC-specific test and test sets.ʻO nā kāne he 95.00% a me 97.83%.ʻOi aku ka kiʻekiʻe o ka helu diagnostic o ke ʻano HIFI ma mua o ka AFP i ka hoʻokaʻawale ʻana i ka HCC mai ka cirrhosis.Eia kekahi, hoʻohana ʻia ka ctDNA i ka mālama ʻana.ʻO Atsushi et al.ua hoʻoholo i nā pae serum preoperative o ka ctDNA i nā maʻi me ka HCC a ua ʻike ʻo ka nui o ka hoʻi hou ʻana a me ka nui o ka metastasis extrahepatic i loko o ka cDNA maikaʻi pūʻulu i ʻoi aku ka kiʻekiʻe ma mua o ka pūʻulu ʻino cDNA, a ua pili nui nā pae cDNA.me ka piʻi ʻana o ke koko.51 No ka mea he biomarker koʻikoʻi loa, hiki i ka ctDNA ke wānana i ka hiki o HCC ke hoʻouka i nā moku.ʻO Wang et al.hana holoʻokoʻa genome sequencing o 46 maʻi me ka HCC, a me ka multivariate anamanaʻo hōʻike i ka paepae ai waiwai o ka allele alapine o ka cDNA likeʻole no ka invasion i microvessels he 0.83%, sensitivity 89.7% a me ka kiko'ī 80.0%.he kumu pilikia kūʻokoʻa no ka hoʻouka ʻana o ka microvascular i ka HCC hiki ke hoʻihoʻi ʻia, e manaʻo ana e kōkua paha ka cDNA i ke alakaʻi ʻana i ka mālama maikaʻi loa.I ka hopena, hoʻopili piha ʻia ka ctDNA i ka hanana a me ka hoʻomohala ʻana o ka HCC a hiki ke hoʻohana ʻia no ka nānā mua ʻana, loiloi loiloi, a me ka nānā ʻana i nā maʻi.
ʻO nā CTC he mau pūnaewele ʻino i loaʻa mai i nā maʻi maʻi mua a i ʻole nā ​​metastases e hoʻokaʻawale i ke kahe koko.Hoʻokuʻu ʻia nā matrix metalloproteinases (MMPs), ka mea e wāwahi ai i ka membrane basement, e ʻae ana i nā cell tumor e komo pololei i ke koko a me nā kīʻaha lymph.Eia naʻe, hoʻopau koke ʻia ka hapa nui o nā CTC e nā anoikis, immune attack, a i ʻole shear stress.53 ʻO ka epithelial-mesenchymal transition (EMT) hiki ke hoʻokaʻawale koke ʻia nā CTC mai ka ʻiʻo tumo mua, hoʻouka i nā capillaries, a loaʻa i ka hoʻomaikaʻi maikaʻi ʻana i ke ola, metastasis, invasiveness, a me ka pale ʻana i ka lāʻau.Ua hōʻike ʻia nā haʻawina he heterogeneity hohonu ma waena o nā ʻano ʻokoʻa like ʻole i nā maʻi maʻi metastatic mua.No laila, hiki i ka loiloi CTC ke alakaʻi i kahi ʻike piha o ka heterogeneity cell tumor.54
ʻO nā hōʻailona kikoʻī no nā CTC pili i ka HCC he glypican-3 (GPC3), asialoglycoprotein receptor (ASGPR), epithelial cell adhesion mole (EpCAM) a me nā mea hōʻailona pili pū me ka CD44, CD90, 55 a me intercellular adhesion mole 1 (ICAM1).) .56 ʻO ka marker GPC3 he protein i hoʻopaʻa ʻia i ka membrane cell i hoʻohana ʻia no ka nānā ʻana i nā pathological a me ke ʻano o ka HCC.57 ʻOi aku ka maʻamau o ka hōʻike ʻana o GPC3 i loko o nā pūnana tumo HCC me ka ʻokoʻa waena a haʻahaʻa a hoʻoikaika i ka neʻe ʻana o ka extrahepatic;Eia kekahi, ʻo ka hele ʻana o GPC3 + ​​CTC e hōʻike ana i ka HCC metastatic.58 ʻO ka ASGPR kahi protein transmembrane i hōʻike ʻia ma ka ʻili o nā hepatocytes a ua hōʻike nui ʻia i ka HCC maikaʻi.ʻO EpCAM kekahi o nā protein pili i ka membrane i hoʻohana pinepine ʻia e hopu i nā CTC.Ua ʻike ʻia ʻo EpCAM ma ke ʻano he hōʻailona ʻili o nā pūnaewele HCC me nā hiʻohiʻona stem cell, 59 e pili ana me nā hiʻohiʻona clinicopathological like ʻole o HCC, e like me ka hoʻouka kaua ʻana, loiloi ʻia nā pae AFP, a me ka pae kiʻekiʻe o ka maʻi maʻi ate ma ka Halemai Barcelona (BCLC).ʻO ka 60 CTC EMT phenotype he metastatic kiʻekiʻe.54 EMT kaʻina hana i loko o ka CTC paipai HCC metastasis.Ua aʻo ʻia ka hōʻike ʻana o nā māka EMT e like me vimentin, twist, E-box zinc finger binding (ZEB) 1, ZEB2, snail, slug, a me E-cadherin i nā CTC i loaʻa i ka ate mai nā maʻi HCC.58 ʻO ka ʻōnaehana CanPatrol™ i hoʻomohala ʻia e Cheng [61] ua hoʻokaʻawale ʻia nā CTC i ʻekolu mau pūʻulu phenotypic e pili ana i nā māka i hōʻike nui ʻia: epithelial phenotype (EpCAM, CK8/18/19), mesenchymal phenotype (vimentin, coiled), a me nā phenotypes hui pū ʻia.I nā maʻi 176, ʻoi aku ka nui o ka CTC ma mua o AFP i ka hoʻokaʻawale ʻana i ka HCC mai ka maʻi ate benign.ʻO nā waiwai AUC no ka huina CTC, AFP, a me ka huina CTC a me AFP i hui pū ʻia he 0.774 (95% CI, 0.704–0.834), 0.669 (95% CI, 0.587–0.750), a me 0.821 (95% CI, 0.756–0.886). ).), kēlā me kēia.Hiki i ka hoʻohālikelike CTC e pili ana i ka EMT ke wānana i ka maʻi HCC, ka hoʻi hou ʻana, ka metastasis, a me ka manawa pōkole.
I kēia manawa, ʻo nā ala no ka ʻike ʻana i nā CSC e pili ana i nā ʻano kino a me nā ʻano biological.ʻO nā ʻano hana kino, i ʻōlelo pinepine ʻia ʻo ka hoʻonui ʻana e pili ana i nā waiwai biophysical, e hilinaʻi nui ʻia i nā waiwai kino o ka CSC, e like me ka nui, density, charge, mobility and deformability.Ma muli o nā waiwai kino, aia nā ʻano like ʻole e like me nā ʻōnaehana filtration-based, dielectrophoresis, a me nā mea ʻē aʻe. e like me EpCAM, ASGPR, kanaka epidermal growth factor receptor 2 (HER2), prostate specific antigen (PSA), kanaka pancytokeratin (P-CK) a me carbamoyl phosphate synthase 1 (CPS1).62 ʻO kekahi ʻano ʻē aʻe, i kapa ʻia ʻo ke ʻano hoʻonui ʻole, hoʻohana i ka cytometry kahe e hoʻokaʻawale i nā CTC mai nā leukocytes e pili ana i ka nui a me ka nui o ka nuclear-to-cytoplasmic ratio.I kēia manawa, ʻo ka hoʻāʻo ʻana i ʻae ʻia e FDA no ka ʻike ʻana i nā CTC, ʻo ia ka ʻōnaehana Cell-Search™, e hoʻohana ana i ka hōʻailona ʻili o ka cell EpCAM. Eia nō naʻe, hiki i ka ʻike ʻana i ka CTC ma muli o nā markers hui ke hoʻonui i ka positivity rate.54 ʻO kahi hui o nā antibodies e kūʻē iā ASGPR a me CPS1 i loaʻa i kahi helu ʻike CTC o 91% i nā maʻi HCC.63 Ua hoʻohana ʻo Zhang et al i kahi CTC-Chip me nā antibodies e kūʻē iā ASGPR, P -CK a me CPS1, a hoʻokaʻawale i ka poʻe maʻi HCC mai ka poʻe me ka maʻi ate benign a i ʻole ka maʻi maʻi non-HCC ma ka helu o 100%.64 Ua ʻike ʻia kahi noiʻi a Wang i nā EpCAM + CTCs ma 60% o 42 mau maʻi HCC a loaʻa i nā correlations koʻikoʻi ma waena o nā positivity ʻelua. ka helu a me ka helu o nā CTC me ka TNM stage.65 Guo et al ua hoʻokiʻekiʻe ʻia kahi helu PCR i loaʻa i ka CTC ma 125/171 (73%) maʻi nona ka pae AFP he <20 ng/mL me kahi sensitivity o 72.5% a me kahi kikoʻī o 95.0%, hoʻohālikelike ʻia me 57.0% a me 90.0% no AFP ma kahi ʻoki ʻoki 20 ng/mL.66 Hiki i ka hui pū ʻana o AFP a me CTC ke hoʻomaikaʻi i ka ʻike HCC.45 Manaʻo ʻia he ʻoi aku ka maikaʻi o nā CTC ma mua o AFP i ka nānā mua ʻana o nā hui. i ka pilikia nui no ka HCC. Eia nō naʻe, hiki i ka ʻike ʻana i ka CTC ma muli o nā markers hui ke hoʻonui i ka positivity rate.54 ʻO kahi hui o nā antibodies e kūʻē iā ASGPR a me CPS1 i loaʻa i kahi helu ʻike CTC o 91% i nā maʻi HCC.63 Ua hoʻohana ʻo Zhang et al i kahi CTC-Chip me nā antibodies e kūʻē iā ASGPR, P -CK a me CPS1, a hoʻokaʻawale i ka poʻe maʻi HCC mai ka poʻe me ka maʻi ate benign a i ʻole ka maʻi maʻi non-HCC ma ka helu o 100%.64 Ua ʻike ʻia kahi noiʻi a Wang i nā EpCAM + CTCs ma 60% o 42 mau maʻi HCC a loaʻa i nā correlations koʻikoʻi ma waena o nā positivity ʻelua. ka helu a me ka helu o nā CTC me ka TNM stage.65 Guo et al ua hoʻokiʻekiʻe ʻia kahi helu PCR i loaʻa i ka CTC ma 125/171 (73%) maʻi nona ka pae AFP he <20 ng/mL me kahi sensitivity o 72.5% a me kahi kikoʻī o 95.0%, hoʻohālikelike ʻia me 57.0% a me 90.0% no AFP ma kahi ʻoki ʻoki 20 ng/mL.66 Hiki i ka hui pū ʻana o AFP a me CTC ke hoʻomaikaʻi i ka ʻike HCC.45 Manaʻo ʻia he ʻoi aku ka maikaʻi o nā CTC ma mua o AFP i ka nānā mua ʻana o nā hui. i ka pilikia nui no ka HCC.Eia naʻe, hiki ke hoʻonui i ka helu o nā hopena maikaʻi.54 ʻO ka hui pū ʻana o nā antibodies anti-ASGPR a me CPS1 i loaʻa i ka nui o ka ʻike CTC o 91% i nā maʻi me HCC.63 Zhang et al.ua hoʻohana i kahi CTC-Chip me nā antibodies e kūʻē iā ASGPR, P-CK a me CPS1, a hoʻokaʻawale hoʻi i nā poʻe maʻi me ka HCC mai ka poʻe me ka maʻi ate benign a i ʻole HCC ma kahi o 100%.частота и количество ЦОК со стадией TNM.65 Guo и соавторы обнаружили, что показатель ПЦР, полученный из ЦОК, был повышен у 125/171 (73%) пациентов, у которых уровень АФП был <20 нг/мл с чувствительностью 72,5% и специфичность 95,0% по сравнению с 57,0% и 90,0% для АФП при пороговом уровне 20 нг/мл.66 Комбинация АФП и ЦОК может улучшить обнаружение ГЦК.45 Считается, что ЦОК имеют преимущество перед АФП при раннем скрининге групп. ka pinepine a me ka helu o nā CTC me ka TNM stage.65 Guo et al ua hoʻokiʻekiʻe ʻia ka PCR i loaʻa mai nā CTC i 125/171 (73%) maʻi i loaʻa nā pae AFP <20 ng/mL me kahi sensitivity o 72.5% a me kahi kikoʻī o 95.0% hoʻohālikelike ʻia me 57.0% a me 90.0% no AFP ma kahi pae ʻoki ʻia o 20 ng/mL.66 ʻO ka hui pū ʻana o AFP a me nā CTC hiki ke hoʻomaikaʻi i ka ʻike ʻana o HCC.45 CTCs ua manaʻo ʻia he ʻoi aku ka maikaʻi ma mua o AFP i ka nānā mua ʻana. pūʻulu.me ka pilikia nui o ka HCC.Eia nō naʻe, hiki ke hoʻonui ʻia ka pākēneka o nā hopena maikaʻi i ka ʻike ʻia ʻana o nā CTC.54 Ua loaʻa i kahi hui ʻana o nā antibodies anti-ASGPR a me CPS1 i kahi 91% CTC ʻike helu i nā maʻi me HCC.63 Zhang et al.Ua hoʻohana ʻo CTC chips me nā antibodies e kūʻē i ka ASGPR, P-CK a me CPS1 a me nā mea maʻi ʻokoʻa me ka HCC mai ka maʻi ate benign a me ka non-HCC me 100%.64 Ua ʻike ʻo Wang i ka 60% o nā EpCAM+ CTC i 42 mau maʻi HCC a loaʻa kahi pilina koʻikoʻi ma waena o ka hanana a me ka helu o nā CTC ma ke kahua TNM. 65 Guo 等人发现，在AFP 水平<20 ng/mL 的125/171 (73%) 名患者中，CTC 衍生的PCR 评分升高，敏分升高，敏分升高，敏分升高，敏分升高，敏亄名怅中，CTC 衍生的PCR 评分升高，敏分升高，敏分升高，敏亄，9态敏亄，7怅敏亄，5%耶和衍生的PCR为20 ng/mL 时的特异性为57.0% 和90.0%. 65 TO TOO 等人 bis 在 水平 水平 水平 水平 水平 水平 <20 ng / ML 衍生截止 截止 截止 截止 截止 截止截止 截止 截止 截止 为 为 为 为 367.0% 和 90.0% 和 90.0% 和 90.0% 和 90.0% 和 90.0% 和 90.0%.65 ʻO 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. Ua ʻike ʻia i loko o 125/171 (73%) nā mea maʻi me nā pae AFP <20 ng/mL, ua hoʻokiʻekiʻe ʻia nā koina PCR i loaʻa i ka CTC me kahi sensitivity o 72.5% a me kahi kikoʻī o 95.0%, ʻoiai ʻo AFP ma kahi kikoʻī ʻoki ʻia. he 20 ng/mL.ml he 57.0% a me 90.0%.66 Hoʻomaikaʻi ka hui ʻana o ORP a me CTC i ka ʻike ʻana o HCC.Manaʻo ʻia ʻo 45 CTC ma mua o AFP i ka nānā mua ʻana i nā heluna HCC kiʻekiʻe.No laila, no nā hui HCC maikaʻi a kiʻekiʻe hoʻi, pono e hui mau ʻia ka hoʻāʻo ʻana CTC me ka ultrasound a me ka ʻike ʻana o AFP.Eia nō naʻe, manaʻo ʻia nā CTC he mau wānana koʻikoʻi o ka metastasis tumo a me ka hoʻi hou ʻana, a ʻaʻole ʻōlelo kūʻokoʻa ka ʻike ʻana i nā CTC ma ke ʻano he mea hana diagnostic.62 No laila, hiki ke lawelawe ʻo CTC ma ke ʻano he biomarker wānana maikaʻi aʻe ma mua o nā mea hoʻohana ʻē aʻe i kēia manawa. Uaʻikeʻo Zhou et al i nā poʻe maʻi me nā helu kiʻekiʻe o EpCAM + CTCs a me nā pūnaewele T regulatory i hōʻike i ka nui o ka pilikia o ka hoʻonuiʻana i ka HCC, ma mua o ka poʻe me nā helu haʻahaʻa o nā CTC, me ka ratio hoʻi hou o 66.7% vs 10.3% (P <0.001).67 Ua hōʻike ʻia kahi haʻawina like e Zhong et al.68 Eia kekahi, ua ʻike ʻo Qi he 101 o nā maʻi 112 (90.81%) me HCC, me ka poʻe i loaʻa i ka maʻi maʻi mua, ua maikaʻi no nā CTC a ua ʻike ʻia nā nodules HCC liʻiliʻi loa ma hope o 3 i 5 mahina o ka hahai ʻana. Uaʻikeʻo Zhou et al i nā poʻe maʻi me nā helu kiʻekiʻe o EpCAM + CTCs a me nā pūnaewele T hoʻoponopono i hōʻike i ka nui o ka pilikia o ka hoʻonuiʻana i ka HCC ma mua o ka poʻe me nā helu haʻahaʻa o CTC, me ka ratio hoʻi hou o 66.7% vs 10.3% (P <0.001).67 A ʻO ka haʻawina like i hōʻike ʻia e Zhong et al.68 Eia hou, ua ʻike ʻo Qi he 101 o 112 mau maʻi (90.81%) me HCC, me ka poʻe me ka maʻi maʻi mua, he maikaʻi no CTC a ua ʻike ʻia nā nodules HCC liʻiliʻi ma hope o 3 a 5 mahina o ka hahai ʻana. Чжоу и 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. Uaʻikeʻo Zhou et al i nā poʻe maʻi me ka EpCAM + CTC kiʻekiʻe a me nā pūnaewele T regulatory iʻoi aku ka nui o ka pilikia o ka hoʻi houʻana o ka HCC ma mua o ka poʻe me nā CTC haʻahaʻa, me ka helu hoʻi o 66.7% vs 10.3% (P<0.001)67.Ua hana ʻia kahi haʻawina like e Zhong et al.68. Eia kekahi, ua ʻike ʻo Qi he 101 o nā maʻi 112 (90.81%) me ka HCC, me ka poʻe i loaʻa i ka maʻi mua, loaʻa nā CTC, a ua ʻike ʻia nā nodules HCC liʻiliʻi ma hope o 3 a 5 mau mahina o ka hahai ʻana. Zolo 等 人 发现, 与 ctc 数量 数量 相比 Hawaiian 患者患者 更高, "复发率 复发率 为高, 数量 调节性 调节性 调节性高, 数量 调节性 调节性 调节性细胞) 患者 10.13% (p <0.001). Zolo 等人 发现 与 ctc 数量数量 的 患者 细胞, Epin. p <0.001) . . . . . . . . . . . . Чжоу и 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). ʻO Zhou et al.Ua ʻike ʻia nā poʻe maʻi me ka EpCAM + CTC kiʻekiʻe a me nā pūnaewele T hoʻoponopono i ʻoi aku ka kiʻekiʻe o ka hoʻi hou ʻana o ka HCC i hoʻohālikelike ʻia me nā maʻi me ka liʻiliʻi o nā CTC, me nā helu hoʻihoʻi o 66.7% a me 10.3%, kēlā me kēia (P <0.001).Ua hōʻike ʻia kahi haʻawina like e Zhong et al.68 Eia kekahi, ua ʻike ʻo Qi he 101 o 112 mau maʻi HCC (90.81%), me nā maʻi me ka maʻi mua, loaʻa nā hopena CTC maikaʻi a loaʻa nā nodules HCC liʻiliʻi loa ma hope o 3 kipa.Nānā a hiki i 5 mahina.Ua loaʻa pū iā lākou nā CTC i nā maʻi 12 me ka maʻi HBV mau loa a loaʻa i nā maʻi maʻi HCC liʻiliʻi i loko o 5 mau mahina i 2 mau maʻi maikaʻi CTC.69 No laila, hiki ke hoʻohana ʻia nā CTC e wānana i ka HCC, 70 akā hiki ke hoʻohana pinepine ʻia e like me nā biomarkers wānana.
E like me cfDNA, hoʻokuʻu ʻia ka cfRNA i ke kahe koko ma o nā ʻōnaehana like ʻole.ʻO kēia mau molekala i loko o ke koko ʻaoʻao e hōʻike ana i ka ʻiʻo maʻi kanesa o ke kumu.Hoʻohālikelike ʻia i nā māka i ʻike ʻia e nā ʻano non-invasive, ʻoi aku ka ikaika o nā cfRNAs, kikoʻī kikoʻī, a nui i loko o ke kaiapuni extracellular.Ua hōʻike ʻia ke koʻikoʻi a me ka waiwai diagnostic o 71 miRNAs (miRNAs) ma HCC i nā haʻawina he nui.ʻO nā miRNAs he endogenous non-coding RNAs (ncRNAs) e hoʻoponopono i nā hana olaola molecular like ʻole ma ke kāohi ʻana i ka unuhi ʻana o nā RNA messenger target (mRNAs).Aia nā miRNA i loko o nā kino apoptotic i hoʻopili ʻia i nā exosome, akā hiki iā lākou ke hoʻopaʻa paʻa i nā protein serum a me nā lipids i ke koko peripheral a hiki ke hoʻohana ʻia e loiloi i ka HCC.Ua komo nā microRNA i ka hana hou ʻana o ka ate, lipid metabolism, apoptosis, mumū, a me ka hoʻomohala ʻana o HCC.72 ʻO nā miRNA oncogenic e like me miR-21, miR-155 a me miR-221 i ʻike maikaʻi ʻia ma HCC.ʻO ka mea nui, he hana koʻikoʻi ka miR-21 i ka synthesis collagen i ka matrix extracellular a me ka fibrosis a hoʻoikaika i ka hepatocarcinogenesis ma o ka hoʻoulu ʻana i nā cell stem hematopoietic.72,73 Tumor suppressor miRNAs ma HCC me miRNA-122, miRNA-29, ka ʻohana Let-7, a me ka ʻohana miRNA-15.ʻO ka ʻohana Let-7 he nui nā miRNA suppressor tumor e kuhikuhi ana i ka ʻohana RAS.Aia ka ʻohana miR-15 i ka miR-15a, miR-15b, miR-16, miR-195, a me miR-497, he mau kaʻina hoʻohui no kekahi mau mRNA.Eia kekahi, he mea nui nā RNA non-coding lōʻihi (lncRNA) a me nā RNA pōʻai (cirRNAs) no ka nānā mua ʻana o HCC.Hōʻike nā lncRNA i ka papa ākea o nā ncRNA, me nā ncRNA like me mRNA, a komo i ka pathogenesis o nā maʻi kanaka he nui.He kuleana hoʻoponopono nā LncRNA i ka microenvironment ate a me ka maʻi ate mau.74 ʻO nā CircRNA kekahi papa o nā ncRNA me nā hana he nui i ka hoʻoponopono ʻana i ka hōʻike gene.I kēia mau lā, ua manaʻo ʻia nā circRNA he mau mea hana diagnostic no HCC.
ʻO ka RNA manuahi ʻole he kūpaʻa maikaʻi loa, me ka pale ʻana i ka mahana, pH, a me RNase, ka mea e hoʻemi ai i ka hoʻokaʻawale ʻana o fnRNA mai ke koko peripheral me ka hoʻohana ʻana i nā ʻano hoʻomaʻemaʻe RNA maʻamau.ʻO nā ʻano hana maʻamau i hoʻohana ʻia me NGS, microarray a me RT-qPCR.Hiki i ka NGS ke ana i nā microRNA a puni ka genome.Eia nō naʻe, he kumukūʻai kēia ʻano a ʻaʻole i hoʻohālikelike ʻia ka loiloi.ʻO ka ʻokoʻa, ʻo ka RT-qPCR ka maʻalahi, hoʻonui wikiwiki i nā ʻakika nucleic, a hāʻawi i nā pono he nui e like me ke kiʻekiʻe kiʻekiʻe, ʻoi aku ka pololei, ʻoi aku ka nui o ka dynamic range, a me ka koi ʻana i nā mea liʻiliʻi.ʻO Microarrays kahi ʻano hana ʻē aʻe i hoʻohana ʻia no ka ʻike miRNA e pili ana i ka hybridization sensitive a kikoʻī o nā miRNA target me nā probes DNA hoʻohui, 75 akā ʻo ka nānā ʻana o ka ʻikepili microarray e pau ana ka manawa.
Ua hōʻike ʻia ke kaʻapuni ʻana i ka miR-122 a me Let-7 i mea pono i ka hoʻomaʻamaʻa ʻana i ka HCC i ka wā mua ma nā pūʻulu pilikia nui, nā māka i nā maʻi me nā nodules premalignant pili i ka HBV a me ka HCC wā mua.76 Cai et al.Ua ʻike ʻia nā lālā o ka ʻohana Let-7 (miR-92, miR-122, miR-125b, miR-143, miR-192, miR-16, miR-126, a me miR-199a/b) HCC i nā maʻi me ka hepatitis.Hiki i ka ʻohana Let-7 ke lawelawe ma ke ʻano he biomarker surrogate kūpono no ka wānana ʻana i ka hoʻomohala ʻana o ka HCC i nā hui kiʻekiʻe e pili ana i ka maʻi hepatitis C.78 Ua loiloi pū ʻia ka Serum e hoʻopuni ana i ka MiR-107 i ka hoʻomaka ʻana o ka HCC, 79 a ua hōʻike ʻo ia i ka mana maikaʻi i nā heluna nui.Ua hōʻike ʻo Zhou et al e hiki i kahi papa o miRNAs (miR-122, miR-192, miR-21, miR-223, miR-26a, miR-27a a me miR-801) hiki ke hoʻokaʻawale i ka HCC mai ka maʻi hepatitis B (CHB) a me ka cirrhosis. ʻO ka sensitivity he 79.1% a me 75%, a me ka kikoʻī 76.4% a me 91.1%.80 Ma ka HCC pili i ka HBV, ua ʻike mākou ua hoʻemi nui ʻia nā pae miR150 i hoʻohālikelike ʻia me nā mea maʻi HBV mau loa me ka HCC (sensitivity 79.1%, specificity 76.5%).Ua hoʻokiʻekiʻe ʻia ka -224 i ka HCC i hoʻohālikelike ʻia me nā mana olakino, a ua hōʻike nā loiloi subgroup i nā pae kiʻekiʻe o nā maʻi me HCC pili me HBV.ʻO ka maʻi hepatitis B-pili i ka cirrhosis a me nā maʻi HCC i ʻike i kahi papa helu siRNA i loaʻa nā siRNA i hōʻike ʻokoʻa ʻia e hiki ke ʻike iā HCC i nā mana like ʻole;ʻOi aku ka maikaʻi o ka pae AUC ma mua o nā mea manawaleʻa AFP.Ua ʻike lākou he ʻehā miRNA (miR-1972, miR-193a-5p, miR-214-3p, a me miR-365a-3p) hiki ke hoʻokaʻawale i nā maʻi me HCC mai nā maʻi me ka HCC ʻole.ʻElima mau miRNA i hōʻike nui ʻia (miR-122-5p, miR-125b-5p, miR-885-5p, miR-100-5p, a me miR-148a-3p) i manaʻo ʻia he mau maʻi HBV i HCC, cirrhosis, a me CHB biomarkers, ʻoi aku. ʻO ka miR-34a-5p paha he mau biomarkers no ka ate cirrhosis, 85 a he mau biomarkers paha no ka nānā mua ʻana o ka HCC i nā heluna nui.ʻO ka lncRNA i aʻo nui ʻia ma HCC ua hoʻoikaika nui ʻia i ka maʻi maʻi ate (HULC).Ua hōʻike ʻia nā haʻawina ʻē aʻe e hiki ke hoʻohana ʻia ka HULC e holo ana i nā maʻi HCC ma ke ʻano he hōʻailona diagnostic no ka mea ua hoʻonui nui ʻia kēia lncRNA i nā maʻi HCC i hoʻohālikelike ʻia me nā kānaka olakino.71,86 Ma waena o nā lnRNA ʻē aʻe, ua manaʻo ʻia ʻo LINC00152 ka lncRNA diagnostic maikaʻi loa ma muli o kona AUC kiʻekiʻe, ʻike a me ka kikoʻī.86 Ma hoʻokahi haʻawina, ua hoʻonui mālie ʻia ka hōʻike koko peripheral o LINC00152 mai nā mana olakino maʻamau i nā poʻe maʻi me CHB a me ka cirrhosis, a ʻoi aku ka kiʻekiʻe loa ma HCC.Ua hōʻike ʻia nā haʻawina o ka hōʻike ʻana o circSMMARCA5 i ka plasma o nā maʻi me ka HCC i ka emi ʻana o ka hōʻike ʻana i ka HCC mai ka maʻi hepatitis a i ka cirrhosis a me nā maʻi precancerous.87 Ua hōʻoia ʻia ka ʻike ʻana o nā pihi ROC i ka hiki o kēia mau circRNAs i ka hoʻokaʻawale ʻana i nā maʻi me ka hepatitis a i ʻole cirrhosis ate mai ka poʻe me HCC, ʻoi aku ka poʻe me nā pae AFP ma lalo o 200 ng/mL.Eia hou, ua kālailai ʻo Zhu i nā RNA cyclic 13,617 i nā laʻana plasma mai nā maʻi HCC pili i ka HBV a ua hōʻoia ʻia ua hōʻike ʻokoʻa ʻia nā RNA cyclic 6 i ka HCC a me ka cirrhosis pili i ka HBV, e manaʻo ana e pono paha nā cRNAs.nā hōʻailona no ka nānā mua ʻana i nā hui kiʻekiʻe e like me nā mea e pili ana i ka maʻi ate, nā maʻi sclerosis.88
ʻO nā exosome nā vesicles membrane 40-160 nm ke anawaena;hui pū nā vesicle intracellular nui me ka membrane cell a hoʻokuʻu ʻia i loko o ka matrix extracellular.Loaʻa iā lākou nā mea hana he nui, e like me nā lipids, nā protein, RNA a me DNA, a ke pāʻani nei i kahi kuleana nui i ke kamaʻilio ʻana ma waena o nā pūnaewele, ʻo ka HCC a me ka ʻole HCC.Hoʻoponopono ka 89,90 Exosome i ka holomua o ka HCC ma o ka hoʻoulu ʻana i nā fibroblasts hepatocyte a me nā pūnaewele stellate, nā cell immune, nā hepatocytes maʻamau, a me nā cell HCC.91 I loko o ka microenvironment tumo, hoʻopuka nā cell tumor i ka nui o nā exosome i lawe ʻia mai nā maʻi maʻi ʻaʻai a hiki i nā cell i oʻo ʻole, ʻo ia hoʻi ke komo i ka oncogenesis, degradation, a me ka hōʻailona kelepona.92 Ua hōʻike ʻia nā haʻawina e hiki i nā exosome ke hoʻololi i nā oncogenes i nā cell maʻamau i ka wā o nā kaʻina pathological, ʻo ia paha kekahi o nā hana o ka hoʻouka ʻana i ka maʻi tumora a me ka metastasis.93 ʻO ke kuleana o nā exosome i ka holomua ʻana o ka maʻi kanesa he ikaika a kikoʻī paha i ke ʻano maʻi maʻi, 89 Hiki ke hoʻopili ʻia nā Exosome e nā mea pili a mamao paha e hoʻoponopono ai i nā ʻano genes he nui i loko o nā cell loaʻa e pili ana i nā ion kamaʻilio intercellular a me nā pilina microenvironment cellular, hiki paha iā lākou. hoʻopili i ka hōʻailona kelepona a me ka metabolism.94 ʻO nā hiʻohiʻona a me nā hoʻololi ikaika o nā molekele ukana exosome e hōʻike pololei i nā hiʻohiʻona a me nā loli ikaika o nā cell tumor makua, 95 ʻo ia hoʻi ke kumu no ka hoʻohana ʻana i nā exosome i ka maʻi a me ka wānana o ka maʻi kanesa, a me ka wānana ʻana i ka pane ʻana o kēlā me kēia i ka lāʻau anticancer. ..96
ʻO nā ʻano hana keʻena kuʻuna no ka hoʻokaʻawale ʻana a me ka nānā ʻana i nā exosome he paʻakikī, multi-step, a me ka manawa e ʻai ai, me ka ultracentrifugation, kānana, ka nui exclusion chromatography, immunoaffinity hoʻomaʻemaʻe, Western blotting, enzyme-linked immunosorbent assay (ELISA), PCR, a me ka nānā ʻana.ʻO nā ʻōnaehana liʻiliʻi a me nā papa hana lab-on-a-chip e hoʻohana ana i ka micro/nanotechnology e hoʻomohala nui ʻia no ka wikiwiki a maʻalahi i ka noho kaʻawale ʻana o nā exosomes.ʻO ka nanoparticle tracking analysis (NTA) kahi ala i hoʻohana nui ʻia no ka ʻike ʻana i ka nui a me ka neʻe ʻana o nā exosome, me nā ʻano e like me nā nanoparticles magnetic a me polyhydroxyalkanoates.Hiki i nā ʻano microfluidic a me nā electrochemical ke ʻike wikiwiki i nā exosome i nā hua kiʻekiʻe.
He mau hōʻailona koʻikoʻi nā protein exosomal no ka hōʻoia ʻana o ka HCC.Ma ke aʻo ʻana ʻo Arbelaiz, ua hoʻokiʻekiʻe nui ʻia ka pae o 98 RasGAP SH3 binding protein (G3BP) a me ka polymeric immunoglobulin receptor (PIGR) i nā exosomes i loaʻa i ka HCC, a ʻoi aku ka maikaʻi o ka hui pū ʻana o nā protein ʻelua ma mua o ka AFP.He mea koʻikoʻi ka nui o ka hao i ka ulu ʻana o ka HCC.Ua hōʻike ʻo Tseng he mea nui paha ka hepcidin i ke kūʻē ʻana i ka HCC.ʻO 99 Exosome i loaʻa mai ka sera o nā maʻi HCC he helu kope kiʻekiʻe aʻe o nā ʻano hepcidin mRNA ma mua o ko lākou mau hoa olakino, e manaʻo ana he ʻano biomarker diagnostic hou no ka HCC.ʻO ka protein 14-3-3ζ i loko o nā exosome i hana ʻia e 100 HCC hiki ke hōʻemi i ka hoʻoulu ʻana o ka cell T, proliferation, a me ka hoʻokaʻawale ʻana a hiki ke hoʻoulu i ka hoʻololi ʻana o T cell i loko o nā pūnae T hoʻoponopono, e hopena i ka pau ʻana o ka cell T.101 Kākoʻo ʻia kēia e kekahi mau noiʻi e noiʻi ana i ka pale ʻana i ka maʻi maʻi mai ka nānā ʻana i ka immune, 102 hiki ke kōkua i ka HCC tumorigenesis.
Ma waho aʻe o ka loaʻa ʻana o ka ecRNA i loko o ka plasma a i ʻole serum, hiki ke hoʻohana ʻia nā exosome i hoʻonui ʻia i ka RNA no ka non-invasive real-time staging i ka nānā mua ʻana i ka maʻi tumora a no ka hoʻoholo ʻana i ka ulu ʻana o ka tumo a me ka pane ʻana i ka lāʻau lapaʻau.ʻO ke kiʻekiʻe o ka exosomal miRNA-21 i loko o ka serum koko i loko o ka hui HCC he 2.21 mau manawa kiʻekiʻe ma mua o ka hui CHB, a ma ka hui HCC he 5.57 manawa kiʻekiʻe ma mua o ka heluna olakino.Ma ka noiʻi Wang, hoʻonui nui ʻia nā exosome i ka HCC i hoʻohālikelike ʻia me nā mea maʻi cirrhotic me nā waiwai AUC o 0.83 (95% CI 0.74-0.93) a me 0.94 (95% CI 0.88-1.00).104 ʻO ka ʻikepili i loaʻa e wehewehe i ke komo ʻana o nā molekole ukana exosomal kūikawā i ka hoʻoponopono o ka oncogenesis a me ka holomua HCC.105 Kūlike ka ʻōlelo serum o miR-221, miR-103, miR-181c, miR-181a, miR-93 a me miR-26a.a me ka metastasis, a me na pae miR21 i oi aku ka kiekie o na ma'i HCC ma mua o na hooponopono ola kino a me na ma'i CHB.102 LncRNA loa'a ka waiwai diagnostic ma HCC.Ua hōʻike ʻia nā haʻawina i loaʻa nā exosome i loaʻa mai ka sera o nā maʻi HCC i nā pae kiʻekiʻe loa o LINC00161, LINC000635, a me ka lncRNA i hoʻāla ʻia e ka hoʻololi ʻana i ka factor-β ma mua o nā mea maʻi me ka HCC ʻole, a ua pili ikaika kēia mau lncRNA me ka pae TNM a me ka nui o ka tumora.110 Conigliaro et al.Ua ʻike ʻia nā CD90+ exosome e hōʻike i nā kiʻekiʻe kiʻekiʻe o lncRNAH19, ka mea i hoʻonui nui i ka hoʻokuʻu ʻana o ka endothelial growth factor (VEGF) a me VEGF-R1 receptor production, ma laila e hoʻoulu ai i ka angiogenesis.93 ʻO nā CircRNA kekahi ʻano o nā ncRNA exosomal - i hōʻike ʻia ma nā pae haʻahaʻa akā paʻa ma waena o nā ʻano, hōʻike pū nā circRNAs i ke ʻano kikoʻī no ke ʻano cell, ʻano kiko, ka pae hoʻomohala, a me ka hana hoʻoponopono.ʻO 111 circRNAs he mau biomarkers diagnostic no ka maʻi maʻi maʻi mua a me ka liʻiliʻi.112 Ua hōʻike ʻia nā hoʻokolohua lapaʻau hou ʻaʻole kūpono ke kikoʻī o kēlā me kēia miRNA i ka wānana HCC.No laila, ʻo ka ʻike paʻakikī me ka hoʻohana ʻana i nā hoʻokolohua lehulehu (e laʻa, miR-122 a me miR-48a i hui pū ʻia me AFP) hiki ke hoʻomaikaʻi i ka ʻike ʻana o ka HCC mua a me ka hoʻokaʻawale ʻana o ka HCC mai ka cirrhosis.100
ʻO nā maʻi me CHB a me ka maʻi cirrhosis ka mea maʻamau o ka hui nui no ka hoʻomohala ʻana i ka HCC.No nā hui koʻikoʻi nui, i ka manawa i loaʻa ai kahi pane virological hoʻomau, pono e hoʻomohala ʻia kahi hoʻolālā mākaʻikaʻi kumu kūʻai e pili ana i ka pilikia o ka HCC, a ʻo ka nānā mua ʻana ke kī i ka hoʻomaikaʻi ʻana i ka maʻi a me ka mālama ʻana i ka HCC me ka ratio kiʻekiʻe o ke kumu kūʻai. ..He nui nā palena o ka nānā ʻana i ka maʻi kanesa: ʻaʻole i hoʻomohala ʻia nā ʻano hoʻomaʻamaʻa hoʻomaka mua no ka hapa nui o nā ʻano maʻi kanesa, a he haʻahaʻa loa ka pili.Ke hoʻohālikelike ʻia me nā ʻano hana hoʻomaʻamaʻa maʻamau, ʻike ʻia ka ʻenehana biopsy wai: maʻalahi o ka laʻana, ʻike panrac, hiki ke hoʻihoʻi hou ʻia, a me ka pane kūpono i ka heterogeneity tumor.Ma muli o ke kumukūʻai kūpono o nā ʻano e pili ana i ka biopsy wai, ʻaʻole i hoʻāʻo mau ʻia kā lākou hoʻohana ʻana i ka nānā ʻana i ka HCC.ʻOiai ka holomua o ka ʻike pololei ʻana ma ka pae molekala, ʻoi aku ke kumu kūʻai o ka biopsy wai no ka ʻike ʻana i ka HCC i nā maʻi i hoʻopaʻa ʻia, e kaupalena ana i kāna hoʻohana ākea e hoʻohālikelike ʻia me nā kaʻina hana kiʻi kikoʻī e like me ke ultrasound a me ka magnetic resonance imaging.113,114 Eia naʻe, ua hōʻike ʻia kahi noiʻi mua e hōʻike ana ka biopsy wai i ka pōmaikaʻi nui ma ke ʻano o nā makahiki ola hoʻoponopono maikaʻi (QALYs).115 Ua hōʻike pū ʻia nā pōmaikaʻi o ka biopsy wai i ka carcinoma mua o ka ʻōpū a me ka nasopharynx.116,117 ʻO ka manaʻo i kēia manawa ʻo ka biopsy wai hiki ke hoʻokō i nā biomarkers serum a me ka nānā ʻana i ka radiological i ka ʻike ʻana a me ka ʻike ʻana i nā maʻi maʻi.117 118
Wahi a nā moʻolelo o kēia manawa, ua hōʻike ʻia ka ʻenehana biopsy wai i ke ʻano kiʻekiʻe o ka naʻau a me ka kikoʻī i ka nānā mua ʻana o nā pūʻulu kiʻekiʻe no ka maʻi maʻi ate.Ma waho o ke ʻano o ka wai biopsy, hiki iā ia ke hoʻokaʻawale i ka HCC mai nā poʻe kiʻekiʻe me ka ʻole o ka HCC, e hōʻike ana i ke koʻikoʻi o ka nānā mua ʻana no ka mea ʻike ʻia nā ʻokoʻa ma waena o nā poʻe kiʻekiʻe a me nā kānaka olakino.He pōkole ka hapalua o ke ola o ka ctDNA a hiki ke hoʻohana ʻia no ka ʻike ʻana i ka HCC, no laila hiki i nā hoʻololi ʻana i ka cDNA i loaʻa i ka tumo ke hāʻawi i nā hōʻike paʻa i ka manawa maoli o ka piʻi ʻana o ka maʻi maʻi, ʻoi aku ka nui o nā maʻi maʻi liʻiliʻi.ʻO ke kiʻekiʻe kiʻekiʻe o ka ctDNA e hōʻike ana i ka ulu ʻana a me ka hoʻolaha ʻana o ka maʻi kanesa a he hōʻailona mua ia o ka holomua a me ka hoʻi hou ʻana.Eia kekahi, ma muli o nā hopena o ka ctDNA, hiki i nā maʻi ke loaʻa i ka mālama pilikino a me ka hahai ʻana.119 ʻOi aku ka maikaʻi o nā pae methylation kikoʻī ma mua o AFP no ka ʻike mua ʻana i ka HCC a me nā nodules cirrhotic.I nā hihia hiki ke hoʻihoʻi ʻia o ka HCC, ʻo nā kiʻekiʻe kiʻekiʻe o cDNA e hōʻike ana i ka microvascular invasion a me ka hoʻi hou ʻana o ka postoperative a me ka metastasis.Hoʻololi ʻia ka helu kope me ke ola o nā maʻi me HCC.Hiki ke manaʻo ʻia e pili ana ka loiloi cDNA i ka mālama holoʻokoʻa o ka HCC, a hiki i ka cDNA ke lilo i hōʻailona kūpono o ka modulation therapeutic.Hoʻokumu ʻia nā māka e pili ana i nā hoʻololi genetic kikoʻī i ka ctDNA e nā alakaʻi alakaʻi e wānana i ka pono a nānā i ke kūʻē ʻana i ka lāʻau.ʻO ka hoʻokolohua ctDNA paha ka mea hana biopsy wai maikaʻi loa no ka nānā mua ʻana.He kuleana koʻikoʻi nō hoʻi nā CTC i ka nānā mua ʻana i nā pūʻulu HCC kiʻekiʻe.ʻO nā hōʻailona like ʻole o nā CTC pili i ka HCC he mea koʻikoʻi i ka hoʻomaka, hoʻomohala ʻana, a me ka hoʻi hou ʻana o HCC.Ma ke ʻano he membrane vesicle, pili nā exosome i nā kamaʻilio intercellular, ʻoi aku hoʻi i nā cell HCC.Paʻa ka microRNA kaʻapuni i ke koko a no laila e ʻoi aku ka maikaʻi no ka nānā mua ʻana i ka HCC.Ua ʻike liʻiliʻi ʻia nā protein exosomal a me nā exosome waiwai nui o RNA, a ua hōʻoia ʻia ko lākou mana wānana no ka HCC.ʻO ka mea mahalo, hiki ke hoʻopili ʻia nā etiologies like ʻole o ka HCC me nā mutation like ʻole, no laila hiki iā mākou ke koho i nā biomarkers like ʻole no ka nānā mua ʻana e pili ana i nā etiologies like ʻole o ka HCC.120
Eia nō naʻe, kānalua nā ʻenehana biopsy wai o kēia manawa ma ke ʻano o ka paʻa a ʻaʻole hiki ke hana kūʻokoʻa i ka nānā mua ʻana a i ʻole ka nānā ʻana i ka HCC, akā hiki ke hoʻokō i ka nānā ʻana a me ka maʻi maʻi.121 Ma ke ʻano o ka biopsy wai, ʻo ka ʻike a me ke kiʻi ʻana o ctDNA, CTC, cfRNA a me exosome-associated AFP a i ʻole PIVKA-II he mau noi hoʻohiki i ka ʻike mua a me ka wānana o HCC.Eia nō naʻe, ʻaʻole e wehewehe ʻia ke ʻano o ka hoʻokuʻu ʻana o ctDNA i ke koko.ʻO ka hōʻike ʻana i nā waiwai olaola kumu o ka ctDNA hiki ke maʻalahi i ka hoʻohana ʻana ma ke ʻano he māka.ʻO ka liʻiliʻi liʻiliʻi o ka ctDNA i ke kahe ʻana a me nā koi hoʻohālike koʻikoʻi i ka hoʻokō ʻana i ka cDNA i ka HCC.Eia kekahi, ʻaʻohe hiʻohiʻona kikoʻī o ka genetic mutations e ʻae i ka ʻike pololei o nā carcinogens.Ma muli o ka nui o nā ʻano genetic a me nā ʻano somatic i loko o nā ʻiʻo maʻamau, ʻo ka hoʻololi ʻana o ka genetic i ʻike ʻia e ka biopsy wai he mea liʻiliʻi paha ia i ka nānā mua ʻana no ka HCC.122 ʻO nā palena o nā pahuhopu gene pono i wehewehe maikaʻi ʻia a me nā biomarkers e kōkua i ka hoʻokaʻawale ʻana i ka cDNA mai ka DNA non-tumor ka mea nui loa i ka hoʻohana ʻana i ka cDNA.nele i ka pono o nā mākaʻikaʻi koʻikoʻi a kikoʻī no ka ʻike ʻana i nā CTC.Loaʻa wale nā ​​​​pūnaewele ola me ka hiki ke metastatic, a ʻaʻole maopopo ka hui maikaʻi o nā māka hoʻonui CSC.ʻO ka hoʻokaʻawale ʻana i nā CTC no ka moʻomeheu a me ka loiloi ʻana i kā lākou ʻaoʻao mutational he hana paʻakikī.Ma muli o nā pilikia me ka ʻike, ka hoʻokaʻawale ʻana a me ka hoʻomaʻemaʻe ʻana i nā exosome, ʻaʻole maopopo ka mīkini molecular kūikawā, a ʻaʻole i hohonu ka noiʻi mua e pili ana i ka mīkini o exosome a me HCC, a me ke ʻano o ka miRNAs, lncRNAs, a me nā protein i hoʻokaʻawale ʻia i exosome. , a ʻaʻole maopopo inā he kaʻina hana kikoʻī ka exosome uptake.ʻO ka hoʻohana ʻana i nā exosome no ka maʻi a me ka mālama ʻana i ka HCC aia nō i ka pae preclinical.ʻO ka nele o ka hoʻohālikelike ʻana i nā kaʻina biopsy wai, e like me ke ʻano o nā paipu i hoʻohana ʻia e hōʻiliʻili i ke koko, ka nui o ke koko, ka waiho ʻana a me ka ʻike ʻana, ka hoʻokaʻawale ʻana a me ka hoʻonui ʻana, hiki ke pale i kā lākou hoʻohana ʻana i ka hana lapaʻau maʻamau ma muli o nā ʻokoʻa o nā hana ma nā kikowaena olakino.ʻO ka maikaʻi o ka biopsy wai i ka nānā mua ʻana, ka hōʻoia, ka loiloi pono, a me ka wānana o ka HCC e hoʻomau ʻia e ʻimi ʻia, ʻoi aku ka nui o nā pūʻulu pilikia.Loaʻa i ka ʻenehana biopsy wai ka mana nui a manaʻo ʻia e hoʻohana nui ʻia i ka hana lapaʻau o ka maʻi maʻi ate i ka wā e hiki mai ana.
1. Sung H., Furley J., Siegel RL et al.Nā helu helu maʻi maʻi maʻi honua 2020: Manaʻo ʻo GLOBOCAN i ka ulu ʻana a me ka make mai 36 mau ʻano maʻi maʻi maʻi ma 185 mau ʻāina.CA Cancer J Clin.2021;71(3):209-249.doi: 10.3322/caac.21660
2. Ke keʻena nui o ka National Health Commission.Paʻa no ka hōʻailona a me ka mālama ʻana i ka maʻi maʻi ate mua (2022 edition) [J].Ka Nūpepa o nā maʻi maʻi ate, 2022, 38 (2): 288-303.doi: 10.3969/j.issn.1001-5256.2022.02.009
3. Zhou J, Sun H, Wang Z, et al.Nā alakaʻi no ka maʻi a me ka mālama ʻana i ka maʻi hepatocellular carcinoma (2019 edition).ʻAʻai maʻi ʻaʻai.2020;9(6):682-720.doi: 10.1159/000509424
4. Kokudo N, Takemura N, Hasegawa K, et al.Nā alakaʻi hoʻomaʻamaʻa lapaʻau no ka maʻi maʻi hepatocellular: Japanese Society for Liver Diseases, 2017 (JSH-HCC 4th guidelines), 2019 update.Waihona ma'i ate.2019;49(10):1109–1113.doi:10.1111/hepr.13411
5. Barrera-Saldana HA, Fernandez-Garza LE, Barrera-Barrera SA Liquid biopsy i ka maʻi o ka ate.Ann Hepato.2021;20:100197.doi:10.1016/j.aohep.2020.03.008
6. Tai TKYu., Tan P.Kh.ʻO ka biopsy maʻi maʻi umauma wai: kahi loiloi i manaʻo ʻia.ʻO Arch Pathol Lab Med.2021;145(6):678–686.doi: 10.5858/arpa.2019-0559-RA
7. Kanval F., Singal AG Surveillance no ka hepatocellular carcinoma: nā hana maikaʻi loa o kēia manawa a me nā kuhikuhi e hiki mai ana.ʻO ka maʻi gastroenterology.2019;157(1):54-64.doi:10.1053/j.gastro.2019.02.049
8. Hui ʻImi ʻEulopa L, Hui ʻEulopa R, C Therapeutics.Nā alakaʻi alakaʻi lapaʻau EASL-EORTC: ka mālama ʻana i ka maʻi hepatocellular carcinoma.J Heparin.2012;56(4):908–943.doi:10.1016/j.jhep.2011.12.001
9. Zhang G., Ha SA, Kim HK et al.ʻO ka loiloi hui pū ʻana o AFP a me HCCR-1 e like me nā māka serological pono i ka carcinoma hepatocellular liʻiliʻi: kahi noiʻi cohort prospective.Dis Mark.2012;32(4):265–271.doi: 10.3233/DMA-2011-0878
10. Chen S, Chen H, Gao S, et al.Hōʻike ʻokoʻa o ka plasma microRNA-125b i ka maʻi hepatitis B pili i ka maʻi a me ka hiki ke diagnostic o ka maʻi hepatocellular i hoʻokomo ʻia i ka maʻi hepatitis B.Waihona ma'i ate.2017;47(4):312-320.doi:10.1111/hepr.12739
11. Halle PR, Foster F., Kudo M. et al.Biology a me ke koʻikoʻi o ka alpha-fetoprotein i ka maʻi hepatocellular carcinoma.ʻO ka ate int.2019;39(12):2214–2229.doi: 10.1111/liv.14223
12. Omata M, Cheng AL, Kokudo N, et al.Nā alakaʻi alakaʻi no ka mālama ʻana i ka carcinoma hepatocellular ma ka ʻāina ʻo Asia-Pacific: 2017 update.Hui Pūʻali no nā maʻi ate.2017;11(4):317–370.doi: 10.1007/s12072-017-9799-9
13. Xu Fei, Zhang Li, He Wei et al.ʻO ka waiwai diagnostic o serum PIVKA-II wale nō a i hui pū ʻia me AFP i nā poʻe maʻi Kina me ka carcinoma hepatocellular.Dis Mark.2021;2021:8868370.doi: 10.1155/2021/8868370
14. Durin L., Praradines A., Basset S. et al.ʻAʻole-liʻiliʻi pūmaʻi akemāmā maʻi 'aʻai non-plasma humoral wai biopsy: kokoke i ke koko!pūʻali koa.2020;9(11).doi: 10.3390/cells9112486
15. Mader S, Pantel K. Liquid biopsy: kūlana o kēia manawa a me nā mea e hiki mai ana.Lapaʻau ʻO Oncol Res.2017;40(7-8):404-408.doi: 10.1159/000478018
16. Palmirotta R, Lovero D, Cafforio P, et al.Biopsy maʻi maʻi maʻi wai: kahi mea hana diagnostic multimodal i ka maʻi oncology.ʻO ka Adv Med Oncol.2018;10:1758835918794630.doi: 10.1177/1758835918794630
17. Mandel P., Metais P. Nucleic acids i loko o ka plasma kanaka.CR Seances Soc Biol Fil.1948;142(3-4):241-243.
18. Mouliere F, Chandrananda D, Piskorz AM, et al.ʻO ka ʻike kiʻekiʻe o ka DNA tumo kaʻapuni ʻana ma o ka nānā ʻana i ka nui o nā ʻāpana.Unuhi ka ʻepekema i ka lāʻau lapaʻau.2018;10:466.doi:10.1126/scitranslmed.aat4921
19. Underhill HR, Kitzman JO, Hellwig C. et al.Kaʻapuni ʻana i ka lōʻihi o ka ʻāpana DNA tumor.Nā genes PLOS.2016;12(7):e1006162.doi:10.1371/journal.pgen.1006162
20. Cheng F, Su L, Qian C. Circulating tumor DNA: he mea hoʻohiki biomarker i ka wai-based cancer biopsy.maʻi puʻupuʻu.2016;7(30):48832–48841.doi:10.18632/oncotarget.9453
21. Bettegovda S., Sauzen M., Leary RJ et al.ʻO ka ʻike ʻana o ka DNA tumora e kaapuni ana i ka wā mua a me ka hope o nā maʻi kino kanaka.Unuhi ka ʻepekema i ka lāʻau lapaʻau.2014;6(224):224ra24.doi:10.1126/scitranslmed.3007094
22. ʻO Mehes G. Liquid biopsy no ka nānā ʻana i ka wānana mutational o ka maʻi maʻi paʻa: ka manaʻo o kahi pathologist.J Hoolaolaola.2019;297:66-70.doi: 10.1016/j.jbiotec.2019.04.002
[PubMed] 23. Lenarts L, Tuveri S, Yatsenko T, et al.ʻO ka ʻike mua ʻana i ka maʻi maʻi ma o ka hoʻolaha ʻana i ka DNA screening plasma: hype a i ʻole manaʻolana?Kānāwai lapaʻau Belgian.2020;75(1):9-1 doi:10.1080/17843286.2019.1671653
24. Nishida N. Ka hopena o ka maʻi hepatitis a me kaʻelemakule ma ka DNA methylation i ka hepatocarcinogenesis kanaka.ʻO ka histopathology.2010;25(5):647–654.doi: 10.14670/HH-25.647