Molecular carcinogenesis of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: One step closer to personalized medicine?

Cell and Bioscience

Volumn 1, Issue 1, 2011, Pages

  Kumar, Mia ^a   Zhao, Xuelian ^a   Wang, Xin W ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 80052874605     PISSN: None     EISSN: 20453701     Source Type: Journal    
DOI: 10.1186/2045-3701-1-5     Document Type: Review

References (134)

1. El-Serag HB, Mason AC. Rising incidence of hepatocellular carcinoma in the United States. N Engl J Med 1999, 340:745-750. 10.1056/NEJM199903113401001, 10072408.
2. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer Clin 2005, 55:74-108.
3. Shaib Y, El-Serag HB. The epidemiology of cholangiocarcinoma. Semin Liver Dis 2004, 24:115-125. 10.1055/s-2004-828889, 15192785.
4. Shaib YH, Davila JA, McGlynn K, El Serag HB. Rising incidence of intrahepatic cholangiocarcinoma in the United States: a true increase?. J Hepatol 2004, 40:472-477. 10.1016/j.jhep.2003.11.030, 15123362.
5. Patel T. Worldwide trends in mortality from biliary tract malignancies. BMC Cancer 2002, 2:10. 10.1186/1471-2407-2-10, 113759, 11991810.
6. Budhu A, Wang XW. The role of cytokines in hepatocellular carcinoma. J Leukoc Biol 2006, 80:1197-1213. 10.1189/jlb.0506297, 16946019.
7. Tardif KD, Waris G, Siddiqui A. Hepatitis C virus, ER stress, and oxidative stress. Trends Microbiol 2005, 13:159-163. 10.1016/j.tim.2005.02.004, 15817385.
8. Bosch FX, Ribes J, Borras J. Epidemiology of primary liver cancer. Semin Liver Dis 1999, 19:271-285. 10.1055/s-2007-1007117, 10518307.
9. Carr BI, Flickinger JC, Lotze MT. Hepatobiliary Cancers: Cancer of the Liver. Cancer Principles & Practice of Oncology 1997, 1087-1114. Rosenberg SA. Philadelphia: Lippincott-Raven, DeVita Jr VT, Hellman S, 5.
10. Taketa K. Alpha-fetoprotein: reevaluation in hepatology. Hepatology 1990, 12:1420-1432. 10.1002/hep.1840120625, 1701754.
11. Kato A, Miyazaki M, Ambiru S, Yoshitomi H, Ito H, Nakagawa K, Shimizu H, Yokosuka O, Nakajima N. Multidrug resistance gene (MDR-1) expression as a useful prognostic factor in patients with human hepatocellular carcinoma after surgical resection. J Surg Oncol 2001, 78:110-115. 10.1002/jso.1129, 11579388.
12. Lazaridis KN, Gores GJ. Cholangiocarcinoma. Gastroenterology 2005, 128:1655-1667. 10.1053/j.gastro.2005.03.040, 15887157.
13. Kornfeld D, Ekbom A, Ihre T. Survival and risk of cholangiocarcinoma in patients with primary sclerosing cholangitis. A population-based study. Scand J Gastroenterol 1997, 32:1042-1045. 10.3109/00365529709011222, 9361178.
14. Thamavit W, Kongkanuntn R, Tiwawech D, Moore MA. Level of Opisthorchis infestation and carcinogen dose-dependence of cholangiocarcinoma induction in Syrian golden hamsters. Virchows Arch B Cell Pathol Incl Mol Pathol 1987, 54:52-58. 10.1007/BF02899196, 2892303.
15. Burak K, Angulo P, Pasha TM, Egan K, Petz J, Lindor KD. Incidence and risk factors for cholangiocarcinoma in primary sclerosing cholangitis. Am J Gastroenterol 2004, 99:523-526. 10.1111/j.1572-0241.2004.04067.x, 15056096.
16. Parkin DM, Srivatanakul P, Khlat M, Chenvidhya D, Chotiwan P, Insiripong S, L'Abbe KA, Wild CP. Liver cancer in Thailand. I. A case-control study of cholangiocarcinoma. Int J Cancer 1991, 48:323-328. 10.1002/ijc.2910480302, 1645697.
17. Kobayashi M, Ikeda K, Saitoh S, Suzuki F, Tsubota A, Suzuki Y, Arase Y, Murashima N, Chayama K, Kumada H. Incidence of primary cholangiocellular carcinoma of the liver in japanese patients with hepatitis C virus-related cirrhosis. Cancer 2000, 88:2471-2477. 10.1002/1097-0142(20000601)88:11<2471::AID-CNCR7>3.0.CO;2-T, 10861422.
18. Sorensen HT, Friis S, Olsen JH, Thulstrup AM, Mellemkjaer L, Linet M, Trichopoulos D, Vilstrup H, Olsen J. Risk of liver and other types of cancer in patients with cirrhosis: a nationwide cohort study in Denmark. Hepatology 1998, 28:921-925. 10.1002/hep.510280404, 9755226.
19. Donato F, Gelatti U, Tagger A, Favret M, Ribero ML, Callea F, Martelli C, Savio A, Trevisi P, Nardi G. Intrahepatic cholangiocarcinoma and hepatitis C and B virus infection, alcohol intake, and hepatolithiasis: a case-control study in Italy. Cancer Causes Control 2001, 12:959-964. 10.1023/A:1013747228572, 11808716.
20. Bergquist A, Glaumann H, Persson B, Broome U. Risk factors and clinical presentation of hepatobiliary carcinoma in patients with primary sclerosing cholangitis: a case-control study. Hepatology 1998, 27:311-316. 10.1002/hep.510270201, 9462625.
21. Chalasani N, Baluyut A, Ismail A, Zaman A, Sood G, Ghalib R, McCashland TM, Reddy KR, Zervos X, Anbari MA, et al. Cholangiocarcinoma in patients with primary sclerosing cholangitis: a multicenter case-control study. Hepatology 2000, 31:7-11. 10.1002/hep.510310103, 10613720.
22. Hussain SP, Hofseth LJ, Harris CC. Radical causes of cancer. Nat Rev Cancer 2003, 3:276-285. 10.1038/nrc1046, 12671666.
23. Bhogal RH, Curbishley SM, Weston CJ, Adams DH, Afford SC. Reactive oxygen species mediate human hepatocyte injury during hypoxia/reoxygenation. Liver Transpl 2010, 16:1303-1313. 10.1002/lt.22157, 21031546.
24. Maki A, Kono H, Gupta M, Asakawa M, Suzuki T, Matsuda M, Fujii H, Rusyn I. Predictive power of biomarkers of oxidative stress and inflammation in patients with hepatitis C virus-associated hepatocellular carcinoma. Ann Surg Oncol 2007, 14:1182-1190. 10.1245/s10434-006-9049-1, 17195915.
25. Chang J, Kim NG, Piao Z, Park C, Park KS, Paik YK, Lee WJ, Kim BR, Kim H. Assessment of chromosomal losses and gains in hepatocellular carcinoma. Cancer Lett 2002, 182:193-202. 10.1016/S0304-3835(02)00083-6, 12048165.
26. Moinzadeh P, Breuhahn K, Stutzer H, Schirmacher P. Chromosome alterations in human hepatocellular carcinomas correlate with aetiology and histological grade--results of an explorative CGH meta-analysis. Br J Cancer 2005, 92:935-941. 10.1038/sj.bjc.6602448, 2361895, 15756261.
27. Thorgeirsson SS, Grisham JW. Molecular pathogenesis of human hepatocellular carcinoma. Nat Genet 2002, 31:339-346. 10.1038/ng0802-339, 12149612.
28. Homayounfar K, Gunawan B, Cameron S, Haller F, Baumhoer D, Uecker S, Sander B, Ramadori G, Lorf T, Fuzesi L. Pattern of chromosomal aberrations in primary liver cancers identified by comparative genomic hybridization. Hum Pathol 2009, 40:834-842. 10.1016/j.humpath.2008.11.005, 19200581.
29. Laurent-Puig P, Legoix P, Bluteau O, Belghiti J, Franco D, Binot F, Monges G, Thomas G, Bioulac-Sage P, Zucman-Rossi J. Genetic alterations associated with hepatocellular carcinomas define distinct pathways of hepatocarcinogenesis. Gastroenterology 2001, 120:1763-1773. 10.1053/gast.2001.24798, 11375957.
30. Nagai H, Pineau P, Tiollais P, Buendia MA, Dejean A. Comprehensive allelotyping of human hepatocellular carcinoma. Oncogene 1997, 14:2927-2933. 10.1038/sj.onc.1201136, 9205099.
31. Wilkens L, Bredt M, Flemming P, Mengel M, Becker T, Klempnauer J, Kreipe H. Comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) in the diagnosis of hepatocellular carcinoma. J Hepatobiliary Pancreat Surg 2002, 9:304-311. 10.1007/s005340200034, 12353141.
32. Wilkens L, Bredt M, Flemming P, Klempnauer J, Heinrich KH. Differentiation of multicentric origin from intra-organ metastatic spread of hepatocellular carcinomas by comparative genomic hybridization. J Pathol 2000, 192:43-51. 10.1002/1096-9896(2000)9999:9999<::AID-PATH671>3.0.CO;2-Z, 10951399.
33. Chen YJ, Yeh SH, Chen JT, Wu CC, Hsu MT, Tsai SF, Chen PJ, Lin CH. Chromosomal changes and clonality relationship between primary and recurrent hepatocellular carcinoma. Gastroenterology 2000, 119:431-440. 10.1053/gast.2000.9373, 10930378.
34. Edamoto Y, Hara A, Biernat W, Terracciano L, Cathomas G, Riehle HM, Matsuda M, Fujii H, Scoazec JY, Ohgaki H. Alterations of RB1, p53 and Wnt pathways in hepatocellular carcinomas associated with hepatitis C, hepatitis B and alcoholic liver cirrhosis. Int J Cancer 2003, 106:334-341. 10.1002/ijc.11254, 12845670.
35. Murakami Y, Hayashi K, Hirohashi S, Sekiya T. Aberrations of the tumor suppressor p53 and retinoblastoma genes in human hepatocellular carcinomas. Cancer Res 1991, 51:5520-5525.
36. Liew CT, Li HM, Lo KW, Leow CK, Chan JY, Hin LY, Lau WY, Lai PB, Lim BK, Huang J, et al. High frequency of p16INK4A gene alterations in hepatocellular carcinoma. Oncogene 1999, 18:789-795. 10.1038/sj.onc.1202359, 9989830.
37. De Souza AT, Hankins GR, Washington MK, Orton TC, Jirtle RL. M6P/IGF2R gene is mutated in human hepatocellular carcinomas with loss of heterozygosity. Nat Genet 1995, 11:447-449. 10.1038/ng1295-447, 7493029.
38. Oka Y, Waterland RA, Killian JK, Nolan CM, Jang HS, Tohara K, Sakaguchi S, Yao T, Iwashita A, Yata Y, et al. M6P/IGF2R tumor suppressor gene mutated in hepatocellular carcinomas in Japan. Hepatology 2002, 35:1153-1163. 10.1053/jhep.2002.32669, 11981765.
39. Laurent-Puig P, Zucman-Rossi J. Genetics of hepatocellular tumors. Oncogene 2006, 25:3778-3786. 10.1038/sj.onc.1209547, 16799619.
40. Hussain SP, Schwank J, Staib F, Wang XW, Harris CC. TP53 mutations and hepatocellular carcinoma: insights into the etiology and pathogenesis of liver cancer. Oncogene 2007, 26:2166-2176. 10.1038/sj.onc.1210279, 17401425.
41. Wong CM, Fan ST, Ng IO. beta-Catenin mutation and overexpression in hepatocellular carcinoma: clinicopathologic and prognostic significance. Cancer 2001, 92:136-145. 10.1002/1097-0142(20010701)92:1<136::AID-CNCR1301>3.0.CO;2-R, 11443619.
42. Miyoshi Y, Iwao K, Nagasawa Y, Aihara T, Sasaki Y, Imaoka S, Murata M, Shimano T, Nakamura Y. Activation of the beta-catenin gene in primary hepatocellular carcinomas by somatic alterations involving exon 3. Cancer Res 1998, 58:2524-2527.
43. Hussain SP, Harris CC. p53 biological network: at the crossroads of the cellular-stress response pathway and molecular carcinogenesis. J Nippon Med Sch 2006, 73:54-64. 10.1272/jnms.73.54, 16641528.
44. Aguilar F, Hussain SP, Cerutti P. Aflatoxin B1 induces the transversion of G-->T in codon 249 of the p53 tumor suppressor gene in human hepatocytes. Proc Natl Acad Sci USA 1993, 90:8586-8590. 10.1073/pnas.90.18.8586, 47402, 8397412.
45. Kirk GD, Lesi OA, Mendy M, Szymanska K, Whittle H, Goedert JJ, Hainaut P, Montesano R. 249(ser) TP53 mutation in plasma DNA, hepatitis B viral infection, and risk of hepatocellular carcinoma. Oncogene 2005, 24:5858-5867. 10.1038/sj.onc.1208732, 16007211.
46. Wang XW, Forrester K, Yeh H, Feitelson MA, Gu JR, Harris CC. Hepatitis B virus X protein inhibits p53 sequence-specific DNA binding, transcriptional activity, and association with transcription factor ERCC3. Proc Natl Acad Sci USA 1994, 91:2230-2234. 10.1073/pnas.91.6.2230, 43344, 8134379.
47. Sheen IS, Jeng KS, Wu JY. Is p53 gene mutation an indicatior of the biological behaviors of recurrence of hepatocellular carcinoma?. World J Gastroenterol 2003, 9:1202-1207.
48. Jeng KS, Sheen IS, Chen BF, Wu JY. Is the p53 gene mutation of prognostic value in hepatocellular carcinoma after resection?. Arch Surg 2000, 135:1329-1333. 10.1001/archsurg.135.11.1329, 11074891.
49. Woo HG, Wang XW, Budhu A, Kim YH, Kwon SM, Tang ZY, Sun Z, Harris CC, Thorgeirsson SS. Association of TP53 Mutations with Stem Cell-Like Gene Expression and Survival of Patients with Hepatocellular Carcinoma. Gastroenterology 2010,
50. Hong H, Takahashi K, Ichisaka T, Aoi T, Kanagawa O, Nakagawa M, Okita K, Yamanaka S. Suppression of induced pluripotent stem cell generation by the p53-p21 pathway. Nature 2009, 460:1132-1135. 10.1038/nature08235, 2917235, 19668191.
51. Derynck R, Akhurst RJ, Balmain A. TGF-beta signaling in tumor suppression and cancer progression. Nat Genet 2001, 29:117-129. 10.1038/ng1001-117, 11586292.
52. Dennis PA, Rifkin DB. Cellular activation of latent transforming growth factor beta requires binding to the cation-independent mannose 6-phosphate/insulin-like growth factor type II receptor. Proc Natl Acad Sci USA 1991, 88:580-584. 10.1073/pnas.88.2.580, 50855, 1846448.
53. Breuhahn K, Vreden S, Haddad R, Beckebaum S, Stippel D, Flemming P, Nussbaum T, Caselmann WH, Haab BB, Schirmacher P. Molecular profiling of human hepatocellular carcinoma defines mutually exclusive interferon regulation and insulin-like growth factor II overexpression. Cancer Res 2004, 64:6058-6064. 10.1158/0008-5472.CAN-04-0292, 15342387.
54. El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 2007, 132:2557-2576. 10.1053/j.gastro.2007.04.061, 17570226.
55. Tang Y, Kitisin K, Jogunoori W, Li C, Deng CX, Mueller SC, Ressom HW, Rashid A, He AR, Mendelson JS, et al. Progenitor/stem cells give rise to liver cancer due to aberrant TGF-beta and IL-6 signaling. Proc Natl Acad Sci USA 2008, 105:2445-2450. 10.1073/pnas.0705395105, 2268156, 18263735.
56. Rebouissou S, Amessou M, Couchy G, Poussin K, Imbeaud S, Pilati C, Izard T, Balabaud C, Bioulac-Sage P, Zucman-Rossi J. Frequent in-frame somatic deletions activate gp130 in inflammatory hepatocellular tumours. Nature 2009, 457:200-204. 10.1038/nature07475, 2695248, 19020503.
57. Chiba T, Zheng YW, Kita K, Yokosuka O, Saisho H, Onodera M, Miyoshi H, Nakano M, Zen Y, Nakanuma Y, et al. Enhanced self-renewal capability in hepatic stem/progenitor cells drives cancer initiation. Gastroenterology 2007, 133:937-950. 10.1053/j.gastro.2007.06.016, 17673212.
58. Clevers H. Wnt/beta-catenin signaling in development and disease. Cell 2006, 127:469-480. 10.1016/j.cell.2006.10.018, 17081971.
59. Kikuchi A. Regulation of beta-catenin signaling in the Wnt pathway. Biochem Biophys Res Commun 2000, 268:243-248. 10.1006/bbrc.1999.1860, 10679188.
60. Yamashita T, Ji J, Budhu A, Forgues M, Yang W, Wang HY, Jia H, Ye Q, Qin LX, Wauthier E, et al. EpCAM-positive hepatocellular carcinoma cells are tumor-initiating cells with stem/progenitor cell features. Gastroenterology 2009, 136:1012-1024. 10.1053/j.gastro.2008.12.004, 2828822, 19150350.
61. Cavard C, Colnot S, Audard V, Benhamouche S, Finzi L, Torre C, Grimber G, Godard C, Terris B, Perret C. Wnt/beta-catenin pathway in hepatocellular carcinoma pathogenesis and liver physiology. Future Oncol 2008, 4:647-660. 10.2217/14796694.4.5.647, 18922122.
62. Chiba T, Kita K, Zheng YW, Yokosuka O, Saisho H, Iwama A, Nakauchi H, Taniguchi H. Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties. Hepatology 2006, 44:240-251. 10.1002/hep.21227, 16799977.
63. Chan KL, Guan XY, Ng IO. High-throughput tissue microarray analysis of c-myc activation in chronic liver diseases and hepatocellular carcinoma. Hum Pathol 2004, 35:1324-1331. 10.1016/j.humpath.2004.06.012, 15668888.
64. Wilkens L, Flemming P, Gebel M, Bleck J, Terkamp C, Wingen L, Kreipe H, Schlegelberger B. Induction of aneuploidy by increasing chromosomal instability during dedifferentiation of hepatocellular carcinoma. Proc Natl Acad Sci USA 2004, 101:1309-1314. 10.1073/pnas.0305817101, 337049, 14745031.
65. Wu KJ, Grandori C, Amacker M, Simon-Vermot N, Polack A, Lingner J, la-Favera R. Direct activation of TERT transcription by c-MYC. Nat Genet 1999, 21:220-224. 10.1038/6010, 9988278.
66. Chang TC, Yu D, Lee YS, Wentzel EA, Arking DE, West KM, Dang CV, Thomas-Tikhonenko A, Mendell JT. Widespread microRNA repression by Myc contributes to tumorigenesis. Nat Genet 2008, 40:43-50. 10.1038/ng.2007.30, 2628762, 18066065.
67. Bjerkvig R, Tysnes BB, Aboody KS, Najbauer J, Terzis AJ. Opinion: the origin of the cancer stem cell: current controversies and new insights. Nat Rev Cancer 2005, 5:899-904. 10.1038/nrc1740, 16327766.
68. Hu TH, Huang CC, Lin PR, Chang HW, Ger LP, Lin YW, Changchien CS, Lee CM, Tai MH. Expression and prognostic role of tumor suppressor gene PTEN/MMAC1/TEP1 in hepatocellular carcinoma. Cancer 2003, 97:1929-1940. 10.1002/cncr.11266, 12673720.
69. Blanco-Aparicio C, Renner O, Leal JF, Carnero A. PTEN, more than the AKT pathway. Carcinogenesis 2007, 28:1379-1386. 10.1093/carcin/bgm052, 17341655.
70. Nakanishi K, Sakamoto M, Yamasaki S, Todo S, Hirohashi S. Akt phosphorylation is a risk factor for early disease recurrence and poor prognosis in hepatocellular carcinoma. Cancer 2005, 103:307-312. 10.1002/cncr.20774, 15593087.
71. He XC, Yin T, Grindley JC, Tian Q, Sato T, Tao WA, Dirisina R, Porter- Westpfahl KS, Hembree M, Johnson T, et al. PTEN-deficient intestinal stem cells initiate intestinal polyposis. Nat Genet 2007, 39:189-198. 10.1038/ng1928, 17237784.
72. Ji J, Wang XW. New kids on the block: Diagnostic and prognostic microRNAs in hepatocellular carcinoma. Cancer Biol Ther 2009, 8:1686-1693.
73. Ji J, Yamashita T, Budhu A, Forgues M, Jia HL, Li C, Deng C, Wauthier E, Reid LM, Ye QH, et al. Identification of microRNA-181 by genome-wide screening as a critical player in EpCAM-positive hepatic cancer stem cells. Hepatology 2009, 50:472-480. 10.1002/hep.22989, 2721019, 19585654.
74. Wang B, Hsu SH, Majumder S, Kutay H, Huang W, Jacob ST, Ghoshal K. TGFbeta-mediated upregulation of hepatic miR-181b promotes hepatocarcinogenesis by targeting TIMP3. Oncogene 2010, 29:1787-1797. 10.1038/onc.2009.468, 2845743, 20023698.
75. Ji J, Zhao L, Budhu A, Forgues M, Jia HL, Qin LX, Ye QH, Yu J, Shi X, Tang ZY, et al. Let-7g targets collagen type I alpha2 and inhibits cell migration in hepatocellular carcinoma. J Hepatol 2010, 52:690-697. 10.1016/j.jhep.2009.12.025, 20338660.
76. Ji J, Shi J, Budhu A, Yu Z, Forgues M, Roessler S, Ambs S, Chen Y, Meltzer PS, Croce CM, et al. MicroRNA expression, survival, and response to interferon in liver cancer. N Engl J Med 2009, 361:1437-1447. 10.1056/NEJMoa0901282, 2786938, 19812400.
77. Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, Patel T. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology 2007, 133:647-658. 10.1053/j.gastro.2007.05.022, 17681183.
78. Jiang J, Gusev Y, Aderca I, Mettler TA, Nagorney DM, Brackett DJ, Roberts LR, Schmittgen TD. Association of MicroRNA expression in hepatocellular carcinomas with hepatitis infection, cirrhosis, and patient survival. Clin Cancer Res 2008, 14:419-427. 10.1158/1078-0432.CCR-07-0523, 2755230, 18223217.
79. Varnholt H. The role of microRNAs in primary liver cancer. Ann Hepatol 2008, 7:104-113.
80. Budhu A, Jia HL, Forgues M, Liu CG, Goldstein D, Lam A, Zanetti KA, Ye QH, Qin LX, Croce CM, et al. Identification of metastasis-related microRNAs in hepatocellular carcinoma. Hepatology 2008, 47:897-907. 10.1002/hep.22160, 18176954.
81. Jones PA, Baylin SB. The fundamental role of epigenetic events in cancer. Nat Rev Genet 2002, 3:415-428. 10.1038/nrg962, 12042769.
82. Lehmann U, Wingen LU, Brakensiek K, Wedemeyer H, Becker T, Heim A, Metzig K, Hasemeier B, Kreipe H, Flemming P. Epigenetic defects of hepatocellular carcinoma are already found in non-neoplastic liver cells from patients with hereditary haemochromatosis. Hum Mol Genet 2007, 16:1335-1342. 10.1093/hmg/ddm082, 17412760.
83. Wong CM, Ng IO. Molecular pathogenesis of hepatocellular carcinoma. Liver Int 2008, 28:160-174. 10.1111/j.1478-3231.2007.01637.x, 18069974.
84. Sakai T, Toguchida J, Ohtani N, Yandell DW, Rapaport JM, Dryja TP. Allele-specific hypermethylation of the retinoblastoma tumor-suppressor gene. Am J Hum Genet 1991, 48:880-888. 1683063, 1673287.
85. Wang L, Wang WL, Zhang Y, Guo SP, Zhang J, Li QL. Epigenetic and genetic alterations of PTEN in hepatocellular carcinoma. Hepatol Res 2007, 37:389-396. 10.1111/j.1872-034X.2007.00042.x, 17441812.
86. Datta J, Kutay H, Nasser MW, Nuovo GJ, Wang B, Majumder S, Liu CG, Volinia S, Croce CM, Schmittgen TD, et al. Methylation mediated silencing of MicroRNA-1 gene and its role in hepatocellular carcinogenesis. Cancer Res 2008, 68:5049-5058. 10.1158/0008-5472.CAN-07-6655, 2562630, 18593903.
87. Furuta M, Kozaki KI, Tanaka S, Arii S, Imoto I, Inazawa J. miR-124 and miR-203 are epigenetically silenced tumor-suppressive microRNAs in hepatocellular carcinoma. Carcinogenesis 2010, 31:766-776. 10.1093/carcin/bgp250, 19843643.
88. Zhang YJ, Wu HC, Shen J, Ahsan H, Tsai WY, Yang HI, Wang LY, Chen SY, Chen CJ, Santella RM. Predicting hepatocellular carcinoma by detection of aberrant promoter methylation in serum DNA. Clin Cancer Res 2007, 13:2378-2384. 10.1158/1078-0432.CCR-06-1900, 17438096.
89. Lee JS, Chu IS, Heo J, Calvisi DF, Sun Z, Roskams T, Durnez A, Demetris AJ, Thorgeirsson SS. Classification and prediction of survival in hepatocellular carcinoma by gene expression profiling. Hepatology 2004, 40:667-676. 10.1002/hep.20375, 15349906.
90. Boyault S, Rickman DS, de Reynies A, Balabaud C, Rebouissou S, Jeannot E, Herault A, Saric J, Belghiti J, Franco D, et al. Transcriptome classification of HCC is related to gene alterations and to new therapeutic targets. Hepatology 2007, 45:42-52. 10.1002/hep.21467, 17187432.
91. Yamashita T, Forgues M, Wang W, Kim JW, Ye Q, Jia H, Budhu A, Zanetti KA, Chen Y, Qin LX, et al. EpCAM and alpha-fetoprotein expression defines novel prognostic subtypes of hepatocellular carcinoma. Cancer Res 2008, 68:1451-1461. 10.1158/0008-5472.CAN-07-6013, 18316609.
92. Yeh SH, Chen PJ, Shau WY, Chen YW, Lee PH, Chen JT, Chen DS. Chromosomal allelic imbalance evolving from liver cirrhosis to hepatocellular carcinoma. Gastroenterology 2001, 121:699-709. 10.1053/gast.2001.27211, 11522754.
93. Aihara T, Noguchi S, Sasaki Y, Nakano H, Imaoka S. Clonal analysis of regenerative nodules in hepatitis C virus-induced liver cirrhosis. Gastroenterology 1994, 107:1805-1811.
94. Yang XR, Xu Y, Yu B, Zhou J, Qiu SJ, Shi GM, Zhang BH, Wu WZ, Shi YH, Wu B, et al. High expression levels of putative hepatic stem/progenitor cell biomarkers related to tumour angiogenesis and poor prognosis of hepatocellular carcinoma. Gut 2010, 59:953-962. 10.1136/gut.2008.176271, 20442200.
95. Haruna Y, Saito K, Spaulding S, Nalesnik MA, Gerber MA. Identification of bipotential progenitor cells in human liver development. Hepatology 1996, 23:476-481. 10.1002/hep.510230312, 8617427.
96. Wu PC, Lai VC, Fang JW, Gerber MA, Lai CL, Lau JY. Hepatocellular carcinoma expressing both hepatocellular and biliary markers also expresses cytokeratin 14, a marker of bipotential progenitor cells. J Hepatol 1999, 31:965-966. 10.1016/S0168-8278(99)80303-1, 10580599.
97. Allen RA, Lisa JR. Combined liver cell and bile duct carcinoma. Am J Pathol 1949, 25:647-655. 1942823, 18152860.
98. Woo HG, Lee JH, Yoon JH, Kim CY, Lee HS, Jang JJ, Yi NJ, Suh KS, Lee KU, Park ES, et al. Identification of a cholangiocarcinoma-like gene expression trait in hepatocellular carcinoma. Cancer Res 2010, 70:3034-3041. 10.1158/0008-5472.CAN-09-2823, 20395200.
99. Fava G. Molecular mechanisms of cholangiocarcinoma. World J Gastrointest Pathophsiol 2010, 1:12-22.
100. Haswell-Elkins MR, Satarug S, Tsuda M, Mairiang E, Esumi H, Sithithaworn P, Mairiang P, Saitoh M, Yongvanit P, Elkins DB. Liver fluke infection and cholangiocarcinoma: model of endogenous nitric oxide and extragastric nitrosation in human carcinogenesis. Mutat Res 1994, 305:241-252.
101. Rosen CB, Nagorney DM, Wiesner RH, Coffey RJ, LaRusso NF. Cholangiocarcinoma complicating primary sclerosing cholangitis. Ann Surg 1991, 213:21-25. 10.1097/00000658-199101000-00004, 1358305, 1845927.
102. Chen MF, Jan YY, Wang CS, Hwang TL, Jeng LB, Chen SC, Chen TJ. A reappraisal of cholangiocarcinoma in patient with hepatolithiasis. Cancer 1993, 71:2461-2465. 10.1002/1097-0142(19930415)71:8<2461::AID-CNCR2820710806>3.0.CO;2-7, 8384069.
103. Jaiswal M, LaRusso NF, Burgart LJ, Gores GJ. Inflammatory cytokines induce DNA damage and inhibit DNA repair in cholangiocarcinoma cells by a nitric oxide-dependent mechanism. Cancer Res 2000, 60:184-190.
104. Sirica AE. Cholangiocarcinoma: molecular targeting strategies for chemoprevention and therapy. Hepatology 2005, 41:5-15. 10.1002/hep.20537, 15690474.
105. Sell S, Dunsford HA. Evidence for the stem cell origin of hepatocellular carcinoma and cholangiocarcinoma. Am J Pathol 1989, 134:1347-1363. 1879951, 2474256.
106. Komuta M, Spee B, Vander BS, De VR, Verslype C, Aerts R, Yano H, Suzuki T, Matsuda M, Fujii H, et al. Clinicopathological study on cholangiolocellular carcinoma suggesting hepatic progenitor cell origin. Hepatology 2008, 47:1544-1556. 10.1002/hep.22238, 18393293.
107. Roskams T. Liver stem cells and their implication in hepatocellular and cholangiocarcinoma. Oncogene 2006, 25:3818-3822. 10.1038/sj.onc.1209558, 16799623.
108. Miller G, Socci ND, Dhall D, D'Angelica M, DeMatteo RP, Allen PJ, Singh B, Fong Y, Blumgart LH, Klimstra DS, et al. Genome wide analysis and clinical correlation of chromosomal and transcriptional mutations in cancers of the biliary tract. J Exp Clin Cancer Res 2009, 28:62. 2698861, 19435499.
109. Koo SH, Ihm CH, Kwon KC, Lee JS, Park JW, Kim JW. Microsatellite alterations in hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Cancer Genet Cytogenet 2003, 146:139-144. 10.1016/S0165-4608(03)00133-X, 14553948.
110. Ding SF, Delhanty JD, Bowles L, Dooley JS, Wood CB, Habib NA. Loss of constitutional heterozygosity on chromosomes 5 and 17 in cholangiocarcinoma. Br J Cancer 1993, 67:1007-1010. 10.1038/bjc.1993.184, 1968440, 8388228.
111. Kang YK, Kim WH, Lee HW, Lee HK, Kim YI. Mutation of p53 and K-ras, and loss of heterozygosity of APC in intrahepatic cholangiocarcinoma. Lab Invest 1999, 79:477-483.
112. Kiba T, Tsuda H, Pairojkul C, Inoue S, Sugimura T, Hirohashi S. Mutations of the p53 tumor suppressor gene and the ras gene family in intrahepatic cholangiocellular carcinomas in Japan and Thailand. Mol Carcinog 1993, 8:312-318. 10.1002/mc.2940080415, 8280380.
113. Qiu SJ, Ye SL, Wu ZQ, Tang ZY, Liu YK. The expression of the mdm2 gene may be related to the aberration of the p53 gene in human hepatocellular carcinoma. J Cancer Res Clin Oncol 1998, 124:253-258. 10.1007/s004320050162, 9645455.
114. Tada M, Omata M, Ohto M. High incidence of ras gene mutation in intrahepatic cholangiocarcinoma. Cancer 1992, 69:1115-1118. 10.1002/cncr.2820690509, 1739910.
115. Furubo S, Harada K, Shimonishi T, Katayanagi K, Tsui W, Nakanuma Y. Protein expression and genetic alterations of p53 and ras in intrahepatic cholangiocarcinoma. Histopathology 1999, 35:230-240. 10.1046/j.1365-2559.1999.00705.x, 10469215.
116. Horie S, Endo K, Kawasaki H, Terada T. Overexpression of MDM2 protein in intrahepatic cholangiocarcinoma: relationship with p53 overexpression, Ki-67 labeling, and clinicopathological features. Virchows Arch 2000, 437:25-30. 10.1007/s004280000201, 10963376.
117. Taniai M, Higuchi H, Burgart LJ, Gores GJ. p16INK4a promoter mutations are frequent in primary sclerosing cholangitis (PSC) and PSC-associated cholangiocarcinoma. Gastroenterology 2002, 123:1090-1098. 10.1053/gast.2002.36021, 12360471.
118. Lee S, Kim WH, Jung HY, Yang MH, Kang GH. Aberrant CpG island methylation of multiple genes in intrahepatic cholangiocarcinoma. Am J Pathol 2002, 161:1015-1022. 10.1016/S0002-9440(10)64262-9, 1867260, 12213730.
119. Tannapfel A, Sommerer F, Benicke M, Weinans L, Katalinic A, Geissler F, Uhlmann D, Hauss J, Wittekind C. Genetic and epigenetic alterations of the INK4a-ARF pathway in cholangiocarcinoma. J Pathol 2002, 197:624-631. 10.1002/path.1139, 12210082.
120. Petmitr S, Pinlaor S, Thousungnoen A, Karalak A, Migasena P. K-ras oncogene and p53 gene mutations in cholangiocarcinoma from Thai patients. Southeast Asian J Trop Med Public Health 1998, 29:71-75.
121. Momoi H, Itoh T, Nozaki Y, Arima Y, Okabe H, Satoh S, Toda Y, Sakai E, Nakagawara K, Flemming P, et al. Microsatellite instability and alternative genetic pathway in intrahepatic cholangiocarcinoma. J Hepatol 2001, 35:235-244. 10.1016/S0168-8278(01)00106-4, 11580146.
122. Rashid A, Ueki T, Gao YT, Houlihan PS, Wallace C, Wang BS, Shen MC, Deng J, Hsing AW. K-ras mutation, p53 overexpression, and microsatellite instability in biliary tract cancers: a population-based study in China. Clin Cancer Res 2002, 8:3156-3163.
123. Berthiaume EP, Wands J. The molecular pathogenesis of cholangiocarcinoma. Semin Liver Dis 2004, 24:127-137. 10.1055/s-2004-828890, 15192786.
124. Meng F, Henson R, Lang M, Wehbe H, Maheshwari S, Mendell JT, Jiang J, Schmittgen TD, Patel T. Involvement of human micro-RNA in growth and response to chemotherapy in human cholangiocarcinoma cell lines. Gastroenterology 2006, 130:2113-2129. 10.1053/j.gastro.2006.02.057, 16762633.
125. Mott JL, Kobayashi S, Bronk SF, Gores GJ. mir-29 regulates Mcl-1 protein expression and apoptosis. Oncogene 2007, 26:6133-6140. 10.1038/sj.onc.1210436, 2432524, 17404574.
126. Poon RT, Fan ST, Lo CM, Liu CL, Wong J. Long-term survival and pattern of recurrence after resection of small hepatocellular carcinoma in patients with preserved liver function: implications for a strategy of salvage transplantation. Ann Surg 2002, 235:373-382. 10.1097/00000658-200203000-00009, 1422443, 11882759.
127. Meza-Junco J, Montano-Loza AJ, Ma M, Wong W, Sawyer MB, Bain VG. Cholangiocarcinoma: has there been any progress?. Can J Gastroenterol 2010, 24:52-57. 2830634, 20186357.
128. Gonzalez B, Denzel S, Mack B, Conrad M, Gires O. EpCAM is involved in maintenance of the murine embryonic stem cell phenotype. Stem Cells 2009, 27:1782-1791. 10.1002/stem.97, 19544432.
129. Yamashita T, Budhu A, Forgues M, Wang XW. Activation of hepatic stem cell marker EpCAM by Wnt-ß-catenin signaling in hepatocellular carcinoma. Cancer Research 2007, 67:10831-10839. 10.1158/0008-5472.CAN-07-0908, 18006828.
130. Ladeiro Y, Couchy G, Balabaud C, Bioulac-Sage P, Pelletier L, Rebouissou S, Zucman-Rossi J. MicroRNA profiling in hepatocellular tumors is associated with clinical features and oncogene/tumor suppressor gene mutations. Hepatology 2008, 47:1955-1963. 10.1002/hep.22256, 18433021.
131. Chung GE, Yoon JH, Myung SJ, Lee JH, Lee SH, Lee SM, Kim SJ, Hwang SY, Lee HS, Kim CY. High expression of microRNA-15b predicts a low risk of tumor recurrence following curative resection of hepatocellular carcinoma. Oncol Rep 2010, 23:113-119. 10.3892/or_00000682, 19956871.
132. Kota J, Chivukula RR, O'donnell KA, Wentzel EA, Montgomery CL, Hwang HW, Chang TC, Vivekanandan P, Torbenson M, Clark KR, et al. Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. Cell 2009, 137:1005-1017. 10.1016/j.cell.2009.04.021, 2722880, 19524505.
133. Maetzel D, Denzel S, Mack B, Canis M, Went P, Benk M, Kieu C, Papior P, Baeuerle PA, Munz M, et al. Nuclear signalling by tumour-associated antigen EpCAM. Nat Cell Biol 2009, 11:162-171. 10.1038/ncb1824, 19136966.
134. Hay N. The Akt-mTOR tango and its relevance to cancer. Cancer Cell 2005, 8:179-183. 10.1016/j.ccr.2005.08.008, 16169463.