KEGG   DISEASE: 肝細胞癌
エントリ  
H00048                                                             

名称    
肝細胞癌;
肝癌
概要    
肝細胞癌 (HCC) は原発性肝癌の主要な型であり、病原学的にウイルスが関係する数少ないヒト新生物のひとつである。HBV/HCV の感染とアルコールやアフラトキシンの摂取の後、遺伝子の変化やエピジェネティックな変化が生じることが示されている。反復性突然変異を生じている遺伝子は、テロメアの維持、TP53、細胞周期調節、Wnt/β-catenin パスウェイ (CTNNB1, AXIN1)、PI3K/AKT/mTOR パスウェイといった多数の重要なドライバーシグナル伝達過程に数多く見られた。全エクソーム解析を用いた最近の研究により、クロマチン再構成 (ARID1A, ARID2) や酸化ストレス (NFE2L2) パスウェイに含まれる新規のドライバー遺伝子において、反復性突然変異が生じていることが明らかにされている。
カテゴリ  
がん
階層分類  
ヒト疾患 [BR:jp08402]
 がん
  消化器系のがん
   H00048  肝細胞癌
ICD-11 による疾患分類 [BR:jp08403]
 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  肝細胞癌
パスウェイ 
hsa05225  肝細胞癌
hsa05203  ウイルス発がん
hsa05161  B型肝炎
hsa05160  C型肝炎
hsa05206  microRNA とがん
ネットワーク
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
  エレメント
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
病因遺伝子 
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]
発癌物質  
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.
病原体   
Hepatitis B virus [GN:T40004]
Hepatitis C virus [GN:T40066]
治療薬   
シクロホスファミド水和物 [DR:D00287]
ニムスチン塩酸塩 [DR:D01059]
フルオロウラシル [DR:D00584]
シタラビン [DR:D00168]
テガフール・ウラシル [DR:D02131]
マイトマイシンC [DR:D00208]
ドキソルビシン塩酸塩 [DR:D01275]
エピルビシン塩酸塩 [DR:D02214]
ミトキサントロン塩酸塩 [DR:D02166]
ソラフェニブトシル酸塩 [DR:D06272]
レゴラフェニブ水和物 [DR:D10137]
カボザンチニブリンゴ酸塩 [DR:D10095]
レンバチニブメシル酸塩 [DR:D09920]
シスプラチン [DR:D00275]
ベバシズマブ [DR:D06409]
ラムシルマブ [DR:D09371]
アテゾリズマブ [DR:D10773]
ミリプラチン水和物 [DR:D06294]
コメント  
ICD-O: 8170/3, Tumor type: Hepatocellular carcinoma (liver cell carcinoma)
リンク   
ICD-11: 2C12.0
ICD-10: C22
MeSH: D006528
文献    
  著者
Kudo M
  タイトル
Signaling pathway and molecular-targeted therapy for hepatocellular carcinoma.
  雑誌
Dig Dis 29:289-302 (2011)
DOI:10.1159/000327562
文献    
  著者
Niu ZS, Niu XJ, Wang WH
  タイトル
Genetic alterations in hepatocellular carcinoma: An update.
  雑誌
World J Gastroenterol 22:9069-9095 (2016)
DOI:10.3748/wjg.v22.i41.9069
文献    
  著者
Breuhahn K, Longerich T, Schirmacher P
  タイトル
Dysregulation of growth factor signaling in human hepatocellular carcinoma.
  雑誌
Oncogene 25:3787-800 (2006)
DOI:10.1038/sj.onc.1209556
文献    
  著者
Whittaker S, Marais R, Zhu AX
  タイトル
The role of signaling pathways in the development and treatment of hepatocellular carcinoma.
  雑誌
Oncogene 29:4989-5005 (2010)
DOI:10.1038/onc.2010.236
文献    
  著者
Minguez B, Tovar V, Chiang D, Villanueva A, Llovet JM
  タイトル
Pathogenesis of hepatocellular carcinoma and molecular therapies.
  雑誌
Curr Opin Gastroenterol 25:186-94 (2009)
DOI:10.1097/MOG.0b013e32832962a1
文献    
  著者
Suriawinata A, Xu R
  タイトル
An update on the molecular genetics of hepatocellular carcinoma.
  雑誌
Semin Liver Dis 24:77-88 (2004)
DOI:10.1055/s-2004-823102
文献    
  著者
Taguchi K, Motohashi H, Yamamoto M
  タイトル
Molecular mechanisms of the Keap1-Nrf2 pathway in stress response and cancer evolution.
  雑誌
Genes Cells 16:123-40 (2011)
DOI:10.1111/j.1365-2443.2010.01473.x
文献    
  著者
Yoo NJ, Kim HR, Kim YR, An CH, Lee SH
  タイトル
Somatic mutations of the KEAP1 gene in common solid cancers.
  雑誌
Histopathology 60:943-52 (2012)
DOI:10.1111/j.1365-2559.2012.04178.x
文献    
  著者
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
  タイトル
Integrated analysis of somatic mutations and focal copy-number changes identifies key genes and pathways in hepatocellular carcinoma.
  雑誌
Nat Genet 44:694-8 (2012)
DOI:10.1038/ng.2256
文献    
  著者
Granito A, Guidetti E, Gramantieri L
  タイトル
c-MET receptor tyrosine kinase as a molecular target in advanced hepatocellular carcinoma.
  雑誌
J Hepatocell Carcinoma 2:29-38 (2015)
DOI:10.2147/JHC.S77038
文献    
  著者
Lee JW, Soung YH, Kim SY, Lee HW, Park WS, Nam SW, Kim SH, Lee JY, Yoo NJ, Lee SH
  タイトル
PIK3CA gene is frequently mutated in breast carcinomas and hepatocellular carcinomas.
  雑誌
Oncogene 24:1477-80 (2005)
DOI:10.1038/sj.onc.1208304
文献    
  著者
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
  タイトル
Exome sequencing of hepatitis B virus-associated hepatocellular carcinoma.
  雑誌
Nat Genet 44:1117-21 (2012)
DOI:10.1038/ng.2391
文献    
  著者
Nault JC, Mallet M, Pilati C, Calderaro J, Bioulac-Sage P, Laurent C, Laurent A, Cherqui D, Balabaud C, Zucman-Rossi J
  タイトル
High frequency of telomerase reverse-transcriptase promoter somatic mutations in hepatocellular carcinoma and preneoplastic lesions.
  雑誌
Nat Commun 4:2218 (2013)
DOI:10.1038/ncomms3218
文献    
PMID:17295177 (gene, tumor type)
  著者
Villanueva A, Newell P, Chiang DY, Friedman SL, Llovet JM.
  タイトル
Genomics and signaling pathways in hepatocellular carcinoma.
  雑誌
Semin Liver Dis 27:55-76 (2007)
DOI:10.1055/s-2006-960171
文献    
PMID:11935086 (gene, tumor type)
  著者
Rocken C, Carl-McGrath S.
  タイトル
Pathology and pathogenesis of hepatocellular carcinoma.
  雑誌
Dig Dis 19:269-78 (2001)
DOI:10.1159/000050693
文献    
PMID:17051452 (tumor type)
  著者
Spangenberg HC, Thimme R, Blum HE.
  タイトル
Serum markers of hepatocellular carcinoma.
  雑誌
Semin Liver Dis 26:385-90 (2006)
DOI:10.1055/s-2006-951606
文献    
  著者
Thorgeirsson SS, Grisham JW.
  タイトル
Molecular pathogenesis of human hepatocellular carcinoma.
  雑誌
Nat Genet 31:339-46 (2002)
DOI:10.1038/ng0802-339
文献    
PMID:15760280 (carcinogen)
  著者
Schottenfeld D, Beebe-Dimmer JL.
  タイトル
Advances in cancer epidemiology: understanding causal mechanisms and the evidence for implementing interventions.
  雑誌
Annu Rev Public Health 26:37-60 (2005)
DOI:10.1146/annurev.publhealth.26.021304.144402
文献    
PMID:15757802 (carcinogen)
  著者
McGlynn KA, London WT.
  タイトル
Epidemiology and natural history of hepatocellular carcinoma.
  雑誌
Best Pract Res Clin Gastroenterol 19:3-23 (2005)
DOI:10.1016/j.bpg.2004.10.004
文献    
PMID:15489140 (carcinogen)
  著者
Wogan GN, Hecht SS, Felton JS, Conney AH, Loeb LA.
  タイトル
Environmental and chemical carcinogenesis.
  雑誌
Semin Cancer Biol 14:473-86 (2004)
DOI:10.1016/j.semcancer.2004.06.010
文献    
PMID:11285186 (carcinogen)
  著者
Smela ME, Currier SS, Bailey EA, Essigmann JM.
  タイトル
The chemistry and biology of aflatoxin B(1): from mutational spectrometry to carcinogenesis.
  雑誌
Carcinogenesis 22:535-45 (2001)
DOI:10.1093/carcin/22.4.535
文献    
PMID:15928434 (carcinogen)
  著者
Khurana S, Dubey ML, Malla N.
  タイトル
Association of parasitic infections and cancers.
  雑誌
Indian J Med Microbiol 23:74-9 (2005)
DOI:10.4103/0255-0857.16044
文献    
PMID:10564925 (carcinogen)
  著者
Nekolla EA, Kellerer AM, Kuse-Isingschulte M, Eder E, Spiess H.
  タイトル
Malignancies in patients treated with high doses of radium-224.
  雑誌
Radiat Res 152:S3-7 (1999)
DOI:10.2307/3580102
文献    
PMID:9498904 (carcinogen)
  著者
Boffetta P, Jourenkova N, Gustavsson P.
  タイトル
Cancer risk from occupational and environmental exposure to polycyclic aromatic hydrocarbons.
  雑誌
Cancer Causes Control 8:444-72 (1997)
DOI:10.1023/a:1018465507029
文献    
PMID:15660110 (carcinogen)
  著者
Luch A.
  タイトル
Nature and nurture - lessons from chemical carcinogenesis.
  雑誌
Nat Rev Cancer 5:113-25 (2005)
DOI:10.1038/nrc1546
文献    
PMID:12556326 (carcinogen)
  著者
Harrison JD, Muirhead CR.
  タイトル
Quantitative comparisons of cancer induction in humans by internally deposited radionuclides and external radiation.
  雑誌
Int J Radiat Biol 79:1-13 (2003)
DOI:10.1080/0955300021000038671
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