Entry |
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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.
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Category |
Cancer
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Brite |
Human diseases [BR:br08402]
Cancers
Cancers of the digestive system
H00048 Hepatocellular carcinoma
Human diseases in ICD-11 classification [BR:br08403]
02 Neoplasms
Malignant neoplasms, except of lymphoid, haematopoietic, central nervous system or related tissues
Malignant neoplasms, stated or presumed to be primary, of specified sites, except of lymphoid, haematopoietic, central nervous system or related tissues
Malignant neoplasms of digestive organs
2C12 Malignant neoplasms of liver or intrahepatic bile ducts
H00048 Hepatocellular carcinoma
Tumor markers [br08442.html]
H00048
Cancer-associated carbohydrates [br08441.html]
H00048
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Pathway |
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Network |
nt06110 MAPK signaling (viruses and bacteria) nt06114 PI3K signaling (viruses) nt06118 TGFB signaling (viruses) nt06119 JAK-STAT signaling (viruses) nt06121 TLR signaling (viruses and bacteria) nt06122 IFN signaling (viruses) nt06123 TNF signaling (viruses and bacteria) nt06124 Chemokine signaling (viruses) nt06130 Cell cycle (viruses) nt06131 Apoptosis (viruses and bacteria) nt06133 RLR signaling (viruses) nt06137 OAS/RNase L pathway (viruses) nt06140 Transcription (viruses) nt06162 Hepatitis B virus (HBV) nt06163 Hepatitis C virus (HCV) nt06263 Hepatocellular carcinoma |
Element |
N00005 | Mutation-activated MET to RAS-ERK signaling pathway |
N00044 | Mutation-activated MET to PI3K signaling pathway |
N00049 | Mutation-activated PI3K to PI3K signaling pathway |
N00052 | Mutation-inactivated PTEN to PI3K signaling pathway |
N00058 | Mutation-activated CTNNB1 to Wnt signaling pathway |
N00059 | FZD7-overexpression to Wnt signaling pathway |
N00071 | Deleted p16(INK4a) to p16-cell cycle G1/S |
N00074 | Loss of RB1 to cell cycle G1/S |
N00115 | Mutation-inactivated TP53 to transcription |
N00228 | TGFA-overexpression to PLCG-PKC signaling pathway |
N00230 | TGFA-overexpression to RAS-ERK signaling pathway |
N00232 | TGFA-overexpression to PI3K signaling pathway |
N00235 | IGF2-overexpression to RAS-ERK signaling pathway |
N00236 | IGF2-overexpression to PI3K signaling pathway |
N00237 | IGF1R-overexpression to RAS-ERK signaling pathway |
N00238 | IGF1R-overexpression to PI3K signaling pathway |
N00240 | TERT-overexpression to telomerase activity |
N00241 | TGFBR2-reduced expression to TGF-beta signaling pathway |
N00242 | Mutation-inactivated AXIN to Wnt signaling pathway |
N00244 | Mutation-inactivated KEAP1 to KEAP1-NRF2 signaling pathway |
N00245 | Mutation-activated NRF2 to KEAP1-NRF2 signaling pathway |
N00246 | HGF-overexpression to RAS-ERK signaling pathway |
N00247 | HGF-overexpression to PI3K signaling pathway |
N00248 | MET-overexpression to RAS-ERK signaling pathway |
N00249 | MET-overexpression to PI3K signaling pathway |
N00267 | HBV HBx to PI3K signaling pathway |
N00268 | HBV HBx to RIG-I-like receptor signaling pathway |
N00269 | HCV core to TNF-NFKB signaling pathway |
N00270 | HCV Core to IFN signaling pathway |
N00271 | HCV NS3/4A to RIG-I-like receptor signaling pathway |
N00272 | HCV NS5A to PI3K signaling pathway |
N00273 | HCV NS5A to oligoadenylate synthetase (OAS)/RNase L pathway |
N00274 | HCV NS5A to RAS-ERK signaling pathway |
N00516 | HCV NS3/4A to TLR3-IRF3 signaling pathway |
N00517 | HCV NS3/4A to TLR3-IRF3 signaling pathway |
N00518 | HCV Core to ERK signaling pathway |
N00519 | HCV Core to ERK signaling pathway |
N00520 | HCV NS5A to p21-cell cycle G1/S |
N00521 | HCV Core to p21-cell cycle G1/S |
N00522 | HCV NS3 to p21-cell cycle G1/S |
N00523 | HCV Core to p21-cell cycle G1/S |
N00524 | HCV NS5A to extrinsic apoptotic pathway |
N00525 | HCV NS5A to TNF-NFKB signaling pathway |
N00526 | HCV NS3 to crosstalk between extrinsic and intrinsic apoptotic pathways |
N00527 | HCV Core to crosstalk between extrinsic and intrinsic apoptotic pathways |
N00528 | HCV core to extrinsic apoptotic pathway |
N00529 | HCV core to RXRA/PPARA-mediated transcription |
N00530 | HCV core to RXRA/LXRA-mediated transcription |
N00531 | HBV HBx to TGF-beta signaling pathway |
N00532 | HBV HBx to Egr-mediated transcription |
N00533 | HBV HBx to Crosstalk between extrinsic and intrinsic apoptotic pathways |
N00534 | HBV HBx to Crosstalk between extrinsic and intrinsic apoptotic pathways |
N00535 | HBV HBx to p53-mediated transcription |
N00537 | HBV HBx to cell cycle G1/S |
N00539 | HBV HBx to Ca2+-PYK2-RAS-ERK signaling pathway |
N00540 | HBV HBx to RAS-ERK signaling pathway |
N00541 | HBV HBx to RAS-ERK signaling pathway |
N00543 | HBV HBx to JNK signaling pathway |
N00544 | HBV HBx to CREB-mediated transcription |
N00545 | HBV HBx to ERK signaling pathway |
N00547 | HBV LHBs to PKC-ERK signaling pathway |
N00548 | HBV HBx to Jak-STAT signaling pathway |
N00549 | HBV HBeAg to TLR2/4-NFKB signaling pathway |
N00550 | HBV HBeAg to TLR2/4-NFKB signaling pathway |
N00551 | HBV HBs to TLR2/4-MAPK signaling pathway |
N00552 | HBV pol to TLR3-IRF3 signaling pathway |
N00554 | HBV HBe to TLR4-IRF3/7 signaling pathway |
N00555 | HBV HBe to TLR4-IRF3/7 signaling pathway |
N00556 | HBV HBe to TLR2/4-NFKB signaling pathway |
N00557 | HBV HBe to TLR2/4-NFKB signaling pathway |
N00558 | HBV pol to IFN signaling pathway |
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Gene |
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Carcinogen |
Aflatoxins (naturally occurring mixtures of) [CPD: C06800]
Alcoholic beverages
Opisthorchis viverrini (infection with)
Radium-224 and its decay products [CPD: C16455]
*Chimney sweeping
*2,3,7,8-Tetrachlorodibenzo-para-dioxin [CPD: C07557]
*Thorium-232 and its decay products, administered intravenously as a colloidal dispersion of thorium232 dioxide
*Tobacco smoking and tobacco smoke
*: Although this is a risk factor for liver cancer in general, the strength of association with different histological tumor types is not well understood.
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Pathogen |
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Drug |
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Comment |
ICD-O: 8170/3, Tumor type: Hepatocellular carcinoma (liver cell carcinoma)
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Other DBs |
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Reference |
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Authors |
Kudo M |
Title |
Signaling pathway and molecular-targeted therapy for hepatocellular carcinoma. |
Journal |
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Reference |
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Authors |
Niu ZS, Niu XJ, Wang WH |
Title |
Genetic alterations in hepatocellular carcinoma: An update. |
Journal |
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Reference |
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Authors |
Breuhahn K, Longerich T, Schirmacher P |
Title |
Dysregulation of growth factor signaling in human hepatocellular carcinoma. |
Journal |
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Reference |
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Authors |
Whittaker S, Marais R, Zhu AX |
Title |
The role of signaling pathways in the development and treatment of hepatocellular carcinoma. |
Journal |
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Reference |
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Authors |
Minguez B, Tovar V, Chiang D, Villanueva A, Llovet JM |
Title |
Pathogenesis of hepatocellular carcinoma and molecular therapies. |
Journal |
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Reference |
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Authors |
Suriawinata A, Xu R |
Title |
An update on the molecular genetics of hepatocellular carcinoma. |
Journal |
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Reference |
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Authors |
Taguchi K, Motohashi H, Yamamoto M |
Title |
Molecular mechanisms of the Keap1-Nrf2 pathway in stress response and cancer evolution. |
Journal |
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Reference |
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Authors |
Yoo NJ, Kim HR, Kim YR, An CH, Lee SH |
Title |
Somatic mutations of the KEAP1 gene in common solid cancers. |
Journal |
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Reference |
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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 |
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Reference |
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Authors |
Granito A, Guidetti E, Gramantieri L |
Title |
c-MET receptor tyrosine kinase as a molecular target in advanced hepatocellular carcinoma. |
Journal |
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Reference |
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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 |
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Reference |
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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 |
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Reference |
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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 |
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Reference |
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Authors |
Villanueva A, Newell P, Chiang DY, Friedman SL, Llovet JM. |
Title |
Genomics and signaling pathways in hepatocellular carcinoma. |
Journal |
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Reference |
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Authors |
Rocken C, Carl-McGrath S. |
Title |
Pathology and pathogenesis of hepatocellular carcinoma. |
Journal |
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Reference |
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Authors |
Spangenberg HC, Thimme R, Blum HE. |
Title |
Serum markers of hepatocellular carcinoma. |
Journal |
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Reference |
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Authors |
Thorgeirsson SS, Grisham JW. |
Title |
Molecular pathogenesis of human hepatocellular carcinoma. |
Journal |
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Reference |
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Authors |
Schottenfeld D, Beebe-Dimmer JL. |
Title |
Advances in cancer epidemiology: understanding causal mechanisms and the evidence for implementing interventions. |
Journal |
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Reference |
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Authors |
McGlynn KA, London WT. |
Title |
Epidemiology and natural history of hepatocellular carcinoma. |
Journal |
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Reference |
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Authors |
Wogan GN, Hecht SS, Felton JS, Conney AH, Loeb LA. |
Title |
Environmental and chemical carcinogenesis. |
Journal |
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Reference |
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Authors |
Smela ME, Currier SS, Bailey EA, Essigmann JM. |
Title |
The chemistry and biology of aflatoxin B(1): from mutational spectrometry to carcinogenesis. |
Journal |
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Reference |
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Authors |
Khurana S, Dubey ML, Malla N. |
Title |
Association of parasitic infections and cancers. |
Journal |
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Reference |
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Authors |
Nekolla EA, Kellerer AM, Kuse-Isingschulte M, Eder E, Spiess H. |
Title |
Malignancies in patients treated with high doses of radium-224. |
Journal |
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Reference |
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Authors |
Boffetta P, Jourenkova N, Gustavsson P. |
Title |
Cancer risk from occupational and environmental exposure to polycyclic aromatic hydrocarbons. |
Journal |
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Reference |
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Authors |
Luch A. |
Title |
Nature and nurture - lessons from chemical carcinogenesis. |
Journal |
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Reference |
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Authors |
Harrison JD, Muirhead CR. |
Title |
Quantitative comparisons of cancer induction in humans by internally deposited radionuclides and external radiation. |
Journal |
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LinkDB |
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