KEGG   DISEASE: Hepatocellular carcinomaHelp
Entry
H00048                      Disease                                

Name
Hepatocellular carcinoma
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
Brite
Human diseases [BR:br08402]
 Cancers
  Cancers of the digestive system
   H00048  Hepatocellular carcinoma
Human diseases in ICD-10 classification [BR:br08403]
 2. Neoplasms (C00-D48)
  C15-C26  Malignant neoplasms of digestive organs
   C22  Malignant neoplasm of liver and intrahepatic bile ducts
    H00048  Hepatocellular carcinoma
Tumor markers [br08442.html]
 H00048
Cancer-accociated carbohydrates [br08441.html]
 H00048
BRITE hierarchy
Pathway
Hepatocellular carcinoma
Viral carcinogenesis
MicroRNAs in cancer
Gene
TGFA (overexpression) [HSA:7039] [KO:K08774]
IGF2 (overexpression) [HSA:3481] [KO:K13769]
IGF1R (overexpression) [HSA:3480] [KO:K05087]
MYC (amplification) [HSA:4609] [KO:K04377]
RB1 (loss) [HSA:5925] [KO:K06618]
TERT (overexpression) [HSA:7015] [KO:K11126]
TP53 (mutation) [HSA:7157] [KO:K04451]
p16 (deletion)  [HSA:1029] [KO:K06621]
PTEN (mutation) [HSA:5728] [KO:K01110]
TGFBR2 (reduced expression) [HSA:7048] [KO:K04388]
FZD7 (overexpression) [HSA:8324] [KO:K02432]
CTNNB1 (mutation) [HSA:1499] [KO:K02105]
AXIN1 (mutation) [HSA:8312] [KO:K02157]
KEAP1 (mutation) [HSA:9817] [KO:K10456]
NFE2L2 (mutation) [HSA:4780] [KO:K05638]
HGF (overexpression) [HSA:3082] [KO:K05460]
MET (mutation, overexpression) [HSA:4233] [KO:K05099]
PIK3CA (mutation) [HSA:5290] [KO:K00922]
ARID1A (mutation) [HSA:8289] [KO:K11653]
ARID2 (mutation) [HSA:196528] [KO:K11765]
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.
Pathogen
Hepatitis B virus [GN:T40004] (chronic infection with)
Hepatitis C virus [GN:T40066] (chronic infection with)
Marker
Alpha-fetoprotein (AFP) [HSA:174] [KO:K16144]
Drug
Doxorubicin [DG:DG00696]
Comment
ICD-O: 8170/3, Tumor type: Hepatocellular carcinoma (liver cell carcinoma)
Other DBs
ICD-10: 
MeSH: 
Reference
PMID:21829020 (description, gene)
  Authors
Kudo M
  Title
Signaling pathway and molecular-targeted therapy for hepatocellular carcinoma.
  Journal
Dig Dis 29:289-302 (2011)
DOI:10.1159/000327562
Reference
PMID:27895396 (description, gene)
  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
Reference
PMID:16799620 (gene)
  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
Reference
PMID:20639898 (gene)
  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
Reference
PMID:19387255 (gene)
  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
Reference
  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
Reference
PMID:21251164 (gene)
  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
Reference
PMID:22348534 (gene)
  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
Reference
PMID:22561517 (gene)
  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
Reference
PMID:27508192 (gene)
  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
Reference
PMID:15608678 (gene)
  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
Reference
PMID:22922871 (gene)
  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
Reference
PMID:23887712 (gene)
  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
Reference
PMID:17295177 (gene, tumor type)
  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
Reference
PMID:11935086 (gene, tumor type)
  Authors
Rocken C, Carl-McGrath S.
  Title
Pathology and pathogenesis of hepatocellular carcinoma.
  Journal
Dig Dis 19:269-78 (2001)
DOI:10.1159/000050693
Reference
PMID:17051452 (tumor type)
  Authors
Spangenberg HC, Thimme R, Blum HE.
  Title
Serum markers of hepatocellular carcinoma.
  Journal
Semin Liver Dis 26:385-90 (2006)
DOI:10.1055/s-2006-951606
Reference
PMID:12149612 (gene)
  Authors
Thorgeirsson SS, Grisham JW.
  Title
Molecular pathogenesis of human hepatocellular carcinoma.
  Journal
Nat Genet 31:339-46 (2002)
DOI:10.1038/ng0802-339
Reference
PMID:15760280 (carcinogen)
  Authors
Schottenfeld D, Beebe-Dimmer JL.
  Title
Advances in cancer epidemiology: understanding causal mechanisms and the evidence for implementing interventions.
  Journal
Annu Rev Public Health 26:37-60 (2005)
DOI:10.1146/annurev.publhealth.26.021304.144402
Reference
PMID:15757802 (carcinogen)
  Authors
McGlynn KA, London WT.
  Title
Epidemiology and natural history of hepatocellular carcinoma.
  Journal
Best Pract Res Clin Gastroenterol 19:3-23 (2005)
DOI:10.1016/j.bpg.2004.10.004
Reference
PMID:15489140 (carcinogen)
  Authors
Wogan GN, Hecht SS, Felton JS, Conney AH, Loeb LA.
  Title
Environmental and chemical carcinogenesis.
  Journal
Semin Cancer Biol 14:473-86 (2004)
DOI:10.1016/j.semcancer.2004.06.010
Reference
PMID:11285186 (carcinogen)
  Authors
Smela ME, Currier SS, Bailey EA, Essigmann JM.
  Title
The chemistry and biology of aflatoxin B(1): from mutational spectrometry to carcinogenesis.
  Journal
Carcinogenesis 22:535-45 (2001)
DOI:10.1093/carcin/22.4.535
Reference
PMID:15928434 (carcinogen)
  Authors
Khurana S, Dubey ML, Malla N.
  Title
Association of parasitic infections and cancers.
  Journal
Indian J Med Microbiol 23:74-9 (2005)
DOI:10.4103/0255-0857.16044
Reference
PMID:10564925 (carcinogen)
  Authors
Nekolla EA, Kellerer AM, Kuse-Isingschulte M, Eder E, Spiess H.
  Title
Malignancies in patients treated with high doses of radium-224.
  Journal
Radiat Res 152:S3-7 (1999)
DOI:10.2307/3580102
Reference
PMID:9498904 (carcinogen)
  Authors
Boffetta P, Jourenkova N, Gustavsson P.
  Title
Cancer risk from occupational and environmental exposure to polycyclic aromatic hydrocarbons.
  Journal
Cancer Causes Control 8:444-72 (1997)
Reference
PMID:15660110 (carcinogen)
  Authors
Luch A.
  Title
Nature and nurture - lessons from chemical carcinogenesis.
  Journal
Nat Rev Cancer 5:113-25 (2005)
DOI:10.1038/nrc1546
Reference
PMID:12556326 (carcinogen)
  Authors
Harrison JD, Muirhead CR.
  Title
Quantitative comparisons of cancer induction in humans by internally deposited radionuclides and external radiation.
  Journal
Int J Radiat Biol 79:1-13 (2003)
DOI:10.1080/0955300021000038671
Reference
  Authors
Papadakis MA and McPhee SJ |(ed)
  Title
Current Medical Diagnosis & Treatment 2015, Fifty-Fourth Edition
  Journal
McGraw Hill Education

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