REFERENCES
2. Bosetti C, Levi F, Boffetta P, Lucchini F, Negri E, et al. Trends in mortality from hepatocellular carcinoma in Europe, 1980-2004. Hepatology 2008;48:137-45.
5. Magee JA, Piskounova E, Morrison SJ. Cancer stem cells: impact, heterogeneity, and uncertainty. Cancer Cell 2012;21:283-96.
7. Haraguchi N, Utsunomiya T, Inoue H, Tanaka F, Mimori K, et al. Characterization of a side population of cancer cells from human gastrointestinal system. Stem Cells Dayt Ohio 2006;24:506-13.
8. Chiba T, Kita K, Zheng YW, Yokosuka O, Saisho H, et al. Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties. Hepatology 2006;44:240-51.
9. Suetsugu A, Nagaki M, Aoki H, Motohashi T, Kunisada T, et al. Characterization of CD133+ hepatocellular carcinoma cells as cancer stem/progenitor cells. Biochem Biophys Res Commun 2006;351:820-4.
10. Ma S, Chan KW, Hu L, Lee TK, Wo JY, et al. Identification and characterization of tumorigenic liver cancer stem/progenitor cells. Gastroenterology 2007;132:2542-56.
11. Yin S, Li J, Hu C, Chen X, Yao M, et al. CD133 positive hepatocellular carcinoma cells possess high capacity for tumorigenicity. Int J Cancer 2007;120:1444-50.
12. Yang ZF, Ngai P, Ho DW, Yu WC, Ng MN, et al. Identification of local and circulating cancer stem cells in human liver cancer. Hepatology 2008;47:919-28.
13. Yang ZF, Ho DW, Ng MN, Lau CK, Yu WC, et al. Significance of CD90+ cancer stem cells in human liver cancer. Cancer Cell 2008;13:153-66.
14. Yamashita T, Ji J, Budhu A, Forgues M, Yang W, et al. EpCAM-positive hepatocellular carcinoma cells are tumor-initiating cells with stem/progenitor cell features. Gastroenterology 2009;136:1012-24.
15. Kimura O, Takahashi T, Ishii N, Inoue Y, Ueno Y, et al. Characterization of the epithelial cell adhesion molecule (EpCAM)+ cell population in hepatocellular carcinoma cell lines. Cancer Sci 2010;101:2145-55.
16. Lee TK, Castilho A, Cheung VC, Tang KH, Ma S, et al. CD24(+) liver tumor-initiating cells drive self-renewal and tumor initiation through STAT3-mediated NANOG regulation. Cell Stem Cell 2011;9:50-63.
17. Haraguchi N, Ishii H, Mimori K, Tanaka F, Ohkuma M, et al. CD13 is a therapeutic target in human liver cancer stem cells. J Clin Invest 2010;120:3326-39.
19. Saitta C, Tripodi G, Barbera A, Bertuccio A, Smedile A, et al. Hepatitis B virus (HBV) DNA integration in patients with occult HBV infection and hepatocellular carcinoma. Liver Int 2015;35:2311-7.
20. Dunsford HA, Sell S, Chisari FV. Hepatocarcinogenesis due to chronic liver cell injury in hepatitis B virus transgenic mice. Cancer Res 1990;50:3400-7.
21. Anfuso B, El-Khobar KE, Ie SI, Avellini C, Radillo O, et al. Activation of hepatic stem cells compartment during hepatocarcinogenesis in a HBsAg HBV-transgenic mouse model. Sci Rep 2018;8:13168.
22. Liu Z, Dai X, Wang T, Zhang C, Zhang W, et al. Hepatitis B virus PreS1 facilitates hepatocellular carcinoma development by promoting appearance and self-renewal of liver cancer stem cells. Cancer Lett 2017;400:149-60.
23. Wang C, Yang W, Yan HX, Luo T, Zhang J, et al. Hepatitis B virus X (HBx) induces tumorigenicity of hepatic progenitor cells in 3,5-diethoxycarbonyl-1,4-dihydrocollidine-treated HBx transgenic mice. Hepatology 2012;55:108-20.
24. Kimura O, Kondo Y, Kogure T, Kakazu E, Ninomiya M, et al. Expression of EpCAM increases in the hepatitis B related and the treatment-resistant hepatocellular carcinoma. Biomed Res Int 2014;2014:172913.
25. Arzumanyan A, Friedman T, Ng IO, Clayton MM, Lian Z, et al. Does the hepatitis B antigen HBx promote the appearance of liver cancer stem cells? Cancer Res 2011;71:3701-8.
26. Li CH, Wang YJ, Dong W, Xiang S, Liang HF, et al. Hepatic oval cell lines generate hepatocellular carcinoma following transfection with HBx gene and treatment with aflatoxin B1 in vivo. Cancer Lett 2011;311:1-10.
27. Ng KY, Chai S, Tong M, Guan XY, Lin CH, et al. C-terminal truncated hepatitis B virus X protein promotes hepatocellular carcinogenesis through induction of cancer and stem cell-like properties. Oncotarget 2016;7:24005-17.
28. Ching RHH, Sze KMF, Lau EYT, Chiu YT, Lee JMF, et al. C-terminal truncated hepatitis B virus X protein regulates tumorigenicity, self-renewal and drug resistance via STAT3/Nanog signaling pathway. Oncotarget 2017;8:23507-16.
29. Fan H, Zhang H, Pascuzzi PE, Andrisani O. Hepatitis B virus X protein induces EpCAM expression via active DNA demethylation directed by RelA in complex with EZH2 and TET2. Oncogene 2015;35:715-26.
30. Zhang X, Liu S, Shen C, Wu Y, Zhang L, et al. DNA methylation consistency implicates the primary tumor cell origin of recurrent hepatocellular carcinoma. Epigenomics 2015;7:581-92.
31. Hamamoto H, Maemura K, Matsuo K, Taniguchi K, Tanaka Y, et al. Delta-like 3 is silenced by HBx via histone acetylation in HBV-associated HCCs. Sci Rep 2018;8:4842.
32. Liu J, Jiang J, Mo J, Liu D, Cao D, et al. Global DNA 5-hydroxymethylcytosine and 5-formylcytosine contents are decreased in the early stage of hepatocellular carcinoma. Hepatology 2018; doi: 10.1002/hep.30146.
33. Shlomai A, de Jong YP, Rice CM. Virus associated malignancies: the role of viral hepatitis in hepatocellular carcinoma. Semin Cancer Biol 2014;26:78-88.
34. Sukowati CH, El-Khobar KE, Ie SI, Anfuso B, Muljono DH, et al. Significance of hepatitis virus infection in the oncogenic initiation of hepatocellular carcinoma. World J Gastroenterol 2016;22:1497-512.
35. Kwon YC, Bose SK, Steele R, Meyer K, Di Bisceglie AM, et al. Promotion of cancer stem-like cell properties in hepatitis C virus-infected hepatocytes. J Virol 2015;89:11549-56.
36. Ali N, Allam H, May R, Sureban SM, Bronze MS, et al. Hepatitis C virus-induced cancer stem cell-like signatures in cell culture and murine tumor xenografts. J Virol 2011;85:12292-303.
37. Bartosch B, Thimme R, Blum HE, Zoulim F. Hepatitis C virus-induced hepatocarcinogenesis. J Hepatol 2009;51:810-20.
38. Machida K, Tsukamoto H, Mkrtchyan H, Duan L, Dynnyk A, et al. Toll-like receptor 4 mediates synergism between alcohol and HCV in hepatic oncogenesis involving stem cell marker Nanog. Proc Natl Acad Sci U S A 2009;106:1548-53.
39. Uthaya Kumar DB, Chen CL, Liu JC, Feldman DE, Sher LS, et al. TLR4 signaling via NANOG cooperates with STAT3 to activate Twist1 and promote formation of tumor-initiating stem-like cells in livers of mice. Gastroenterology 2016;150:707-19.
40. Taniguchi H, Kato N, Otsuka M, Goto T, Yoshida H, et al. Hepatitis C virus core protein upregulates transforming growth factor-beta 1 transcription. J Med Virol 2004;72:52-9.
41. Sasaki R, Devhare P, Ray RB, Ray R. Hepatitis C virus-induced tumor-initiating cancer stem-like cells activate stromal fibroblasts in a xenograft tumor model. Hepatology 2017;66:1766-78.
42. Machida K, Chen CL, Liu JC, Kashiwabara C, Feldman D, et al. Cancer stem cells generated by alcohol, diabetes, and hepatitis C virus. J Gastroenterol Hepatol 2012;27 Suppl 2:19-22.
43. Debebe A, Medina V, Chen CY, Mahajan IM, Jia C, et al. Wnt/β-catenin activation and macrophage induction during liver cancer development following steatosis. Oncogene 2017;36:6020-9.
44. Kwon YC, Sasaki R, Meyer K, Ray R. Hepatitis C virus core protein modulates endoglin (CD105) signaling pathway for liver pathogenesis. J Virol 2017; doi: 10.1128/JVI.01235-17.
45. Fan H, Cui Z, Zhang H, Mani SK, Diab A, et al. DNA demethylation induces SALL4 gene re-expression in subgroups of hepatocellular carcinoma associated with hepatitis B or C virus infection. Oncogene 2017;36:2435-45.
46. Anfuso B, El-Khobar KE, Sukowati CH, Tiribelli C. The multiple origin of cancer stem cells in hepatocellular carcinoma. Clin Res Hepatol Gastroenterol 2015;39 Suppl 1:S92-7.
47. Chen YL, Lin PY, Ming YZ, Huang WC, Chen RF, et al. The effects of the location of cancer stem cell marker CD133 on the prognosis of hepatocellular carcinoma patients. BMC Cancer 2017;17:474.
48. Chan AW, Tong JH, Chan SL, Lai PB, To KF. Expression of stemness markers (CD133 and EpCAM) in prognostication of hepatocellular carcinoma. Histopathology 2014;64:935-50.
49. Sasaki A, Kamiyama T, Yokoo H, Nakanishi K, Kubota K, et al. Cytoplasmic expression of CD133 is an important risk factor for overall survival in hepatocellular carcinoma. Oncol Rep 2010;24:537-46.
50. Ma YC, Yang JY, Yan LN. Relevant markers of cancer stem cells indicate a poor prognosis in hepatocellular carcinoma patients: a meta-analysis. Eur J Gastroenterol Hepatol 2013;25:1007-16.
51. Song W, Li H, Tao K, Li R, Song Z, et al. Expression and clinical significance of the stem cell marker CD133 in hepatocellular carcinoma. Int J Clin Pract 2008;62:1212-8.
52. Sukowati CHC, Anfuso B, Torre G, Francalanci P, Crocè LS, et al. The expression of CD90/Thy-1 in hepatocellular carcinoma: an in vivo and in vitro study. PLoS One 2013;8:e76830.
53. Liu R, Shen Y, Nan K, Mi B, Wu T, et al. Association between expression of cancer stem cell markers and poor differentiation of hepatocellular carcinoma: a meta-analysis (PRISMA). Medicine (Baltimore) 2015;94:e1306.
54. Lingala S, Cui YY, Chen X, Ruebner BH, Qian XF, et al. Immunohistochemical staining of cancer stem cell markers in hepatocellular carcinoma. Exp Mol Pathol 2010;89:27-35.
55. Dai XM, Yang SL, Zheng XM, Chen GG, Chen J, et al. CD133 expression and α-fetoprotein levels define novel prognostic subtypes of HBV-associated hepatocellular carcinoma: a long-term follow-up analysis. Oncol Lett 2018;15:2985-91.
56. Yeh CT, Kuo CJ, Lai MW, Chen TC, Lin CY, et al. CD133-positive hepatocellular carcinoma in an area endemic for hepatitis B virus infection. BMC Cancer 2009;9:324.
57. Lu JW, Chang JG, Yeh KT, Chen RM, Tsai JJ, et al. Overexpression of Thy1/CD90 in human hepatocellular carcinoma is associated with HBV infection and poor prognosis. Acta Histochem 2011;113:833-8.
58. Bose SK, Meyer K, Bisceglie AMD, Ray RB, Ray R. Hepatitis C virus induces epithelial-mesenchymal transition in primary human hepatocytes. J Virol 2012;86:13621-8.
59. Machida K. Existence of cancer stem cells in hepatocellular carcinoma: myth or reality? Hepatol Int 2017;11:143-7.
