| H00048 | |
| H number | H00048 |
| Name | Hepatocellular carcinoma; Liver cancer |
| Description | Hepatocellular carcinoma (HCC) is a major type of primary liver cancer and one of the rare human neoplasms etiologically linked to viral factors. It has been shown that, after HBV/HCV infection and alcohol or aflatoxin B1 exposure, genetic and epigenetic changes occur. The recurrent mutated genes were found to be highly enriched in multiple key driver signaling processes, including telomere maintenance, TP53, cell cycle regulation, the Wnt/beta-catenin pathway (CTNNB1 and AXIN1), the phosphatidylinositol-3 kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway. Recent studies using whole-exome sequencing have revealed recurrent mutations in new driver genes involved in the chromatin remodelling (ARID1A and ARID2) and the oxidative stress (NFE2L2) pathways. |
| Category | Cancer DIS_PATHWAY hsa05225 Hepatocellular carcinoma |
| Network | nt06162 Hepatitis B virus (HBV) nt06163 Hepatitis C virus (HCV) nt06263 Hepatocellular carcinoma nt06505(H00048) WNT signaling nt06507(H00048) TGFB signaling nt06516(H00048) TNF signaling nt06517(H00048) TLR signaling nt06518(H00048) JAK-STAT signaling nt06519(H00048) RLR signaling nt06524(H00048) Apoptosis nt06526(H00048) MAPK signaling nt06528(H00048) Calcium signaling nt06530(H00048) PI3K signaling |
| Gene | TGFA (overexpression) [HSA:7039] [KO:K08774] IGF2 (overexpression) [HSA:3481] [KO:K13769] IGF1R (overexpression) [HSA:3480] [KO:K05087] TERT (overexpression) [HSA:7015] [KO:K11126] FZD7 (overexpression) [HSA:8324] [KO:K02432] HGF (overexpression) [HSA:3082] [KO:K05460] MET (mutation, overexpression) [HSA:4233] [KO:K05099] MYC (amplification) [HSA:4609] [KO:K04377] RB1 (loss) [HSA:5925] [KO:K06618] CDKN2A (deletion) [HSA:1029] [KO:K06621] TGFBR2 (reduced expression) [HSA:7048] [KO:K04388] TP53 [HSA:7157] [KO:K04451] PTEN [HSA:5728] [KO:K01110] CTNNB1 [HSA:1499] [KO:K02105] AXIN1 [HSA:8312] [KO:K02157] KEAP1 [HSA:9817] [KO:K10456] NFE2L2 [HSA:4780] [KO:K05638] PIK3CA [HSA:5290] [KO:K00922] ARID1A [HSA:8289] [KO:K11653] ARID2 [HSA:196528] [KO:K11765] CASP8 [HSA:841] [KO:K04398] IGF2R [HSA:3482] [KO:K06564] |
| Pathogen | Hepatitis B virus [GN:T40004] Hepatitis C virus [GN:T40066] |
| Env factor | - |
| Carcinogen | - |
| Drug | Sorafenib tosylate [DR:D06272] Regorafenib hydrate [DR:D10137] Cabozantinib s-malate [DR:D10095] Lenvatinib mesylate [DR:D09920] Nivolumab [DR:D10316] Pembrolizumab [DR:D10574] Durvalumab [DR:D10808] Atezolizumab [DR:D10773] Bevacizumab [DR:D06409] Ramucirumab [DR:D09371] Ipilimumab [DR:D04603] Tremelimumab [DR:D06657] |
| Comment | - |
| Other DBs | ICD-11: 2C12.0 ICD-10: C22 MeSH: D006528 OMIM: 114550 |
| Reference | PMID:21829020 AUTHORS Kudo M TITLE Signaling pathway and molecular-targeted therapy for hepatocellular carcinoma. JOURNAL Dig Dis 29:289-302 (2011) DOI:10.1159/000327562 PMID:27895396 AUTHORS Niu ZS, Niu XJ, Wang WH TITLE Genetic alterations in hepatocellular carcinoma: An update. JOURNAL World J Gastroenterol 22:9069-9095 (2016) DOI:10.3748/wjg.v22.i41.9069 PMID:16799620 AUTHORS Breuhahn K, Longerich T, Schirmacher P TITLE Dysregulation of growth factor signaling in human hepatocellular carcinoma. JOURNAL Oncogene 25:3787-800 (2006) DOI:10.1038/sj.onc.1209556 PMID:20639898 AUTHORS Whittaker S, Marais R, Zhu AX TITLE The role of signaling pathways in the development and treatment of hepatocellular carcinoma. JOURNAL Oncogene 29:4989-5005 (2010) DOI:10.1038/onc.2010.236 PMID:19387255 AUTHORS Minguez B, Tovar V, Chiang D, Villanueva A, Llovet JM TITLE Pathogenesis of hepatocellular carcinoma and molecular therapies. JOURNAL Curr Opin Gastroenterol 25:186-94 (2009) DOI:10.1097/MOG.0b013e32832962a1 PMID:15085488 AUTHORS Suriawinata A, Xu R TITLE An update on the molecular genetics of hepatocellular carcinoma. JOURNAL Semin Liver Dis 24:77-88 (2004) DOI:10.1055/s-2004-823102 PMID:22922871 AUTHORS Huang J, Deng Q, Wang Q, Li KY, Dai JH, Li N, Zhu ZD, Zhou B, Liu XY, Liu RF, Fei QL, Chen H, Cai B, Zhou B, Xiao HS, Qin LX, Han ZG TITLE Exome sequencing of hepatitis B virus-associated hepatocellular carcinoma. JOURNAL Nat Genet 44:1117-21 (2012) DOI:10.1038/ng.2391 PMID:17295177 AUTHORS Villanueva A, Newell P, Chiang DY, Friedman SL, Llovet JM. TITLE Genomics and signaling pathways in hepatocellular carcinoma. JOURNAL Semin Liver Dis 27:55-76 (2007) DOI:10.1055/s-2006-960171 PMID:11935086 AUTHORS Rocken C, Carl-McGrath S. TITLE Pathology and pathogenesis of hepatocellular carcinoma. JOURNAL Dig Dis 19:269-78 (2001) DOI:10.1159/000050693 PMID:12149612 AUTHORS Thorgeirsson SS, Grisham JW. TITLE Molecular pathogenesis of human hepatocellular carcinoma. JOURNAL Nat Genet 31:339-46 (2002) DOI:10.1038/ng0802-339 PMID:21251164 (KEAP1, NFE2L2) AUTHORS Taguchi K, Motohashi H, Yamamoto M TITLE Molecular mechanisms of the Keap1-Nrf2 pathway in stress response and cancer evolution. JOURNAL Genes Cells 16:123-40 (2011) DOI:10.1111/j.1365-2443.2010.01473.x PMID:22348534 (KEAP1, NFE2L2) AUTHORS Yoo NJ, Kim HR, Kim YR, An CH, Lee SH TITLE Somatic mutations of the KEAP1 gene in common solid cancers. JOURNAL Histopathology 60:943-52 (2012) DOI:10.1111/j.1365-2559.2012.04178.x PMID:22561517 (CTNNB1, AXIN1, ARID1A, ARID2) AUTHORS Guichard C, Amaddeo G, Imbeaud S, Ladeiro Y, Pelletier L, Maad IB, Calderaro J, Bioulac-Sage P, Letexier M, Degos F, Clement B, Balabaud C, Chevet E, Laurent A, Couchy G, Letouze E, Calvo F, Zucman-Rossi J TITLE Integrated analysis of somatic mutations and focal copy-number changes identifies key genes and pathways in hepatocellular carcinoma. JOURNAL Nat Genet 44:694-8 (2012) DOI:10.1038/ng.2256 PMID:27508192 (MET) AUTHORS Granito A, Guidetti E, Gramantieri L TITLE c-MET receptor tyrosine kinase as a molecular target in advanced hepatocellular carcinoma. JOURNAL J Hepatocell Carcinoma 2:29-38 (2015) DOI:10.2147/JHC.S77038 PMID:15608678 (PIK3CA) AUTHORS Lee JW, Soung YH, Kim SY, Lee HW, Park WS, Nam SW, Kim SH, Lee JY, Yoo NJ, Lee SH TITLE PIK3CA gene is frequently mutated in breast carcinomas and hepatocellular carcinomas. JOURNAL Oncogene 24:1477-80 (2005) DOI:10.1038/sj.onc.1208304 PMID:23887712 (TERT) AUTHORS Nault JC, Mallet M, Pilati C, Calderaro J, Bioulac-Sage P, Laurent C, Laurent A, Cherqui D, Balabaud C, Zucman-Rossi J TITLE High frequency of telomerase reverse-transcriptase promoter somatic mutations in hepatocellular carcinoma and preneoplastic lesions. JOURNAL Nat Commun 4:2218 (2013) DOI:10.1038/ncomms3218 PMID:15531912 (CASP8) AUTHORS Soung YH, Lee JW, Kim SY, Sung YJ, Park WS, Nam SW, Kim SH, Lee JY, Yoo NJ, Lee SH TITLE Caspase-8 gene is frequently inactivated by the frameshift somatic mutation 1225_1226delTG in hepatocellular carcinomas. JOURNAL Oncogene 24:141-7 (2005) DOI:10.1038/sj.onc.1208244 PMID:7493029 (IGF2R) AUTHORS De Souza AT, Hankins GR, Washington MK, Orton TC, Jirtle RL TITLE M6P/IGF2R gene is mutated in human hepatocellular carcinomas with loss of heterozygosity. JOURNAL Nat Genet 11:447-9 (1995) DOI:10.1038/ng1295-447 |