REFERENCES
1. Collaboration Global Burden of Disease Liver Cancer, Akinyemiju T, Abera S, Ahmed M, Alam N, et al. The burden of primary liver cancer and underlying etiologies from 1990 to 2015 at the global, regional, and national level: results from the global burden of disease study 2015. JAMA Oncol 2017;3:1683-91.
2. Soerjomataram I, Lortet-Tieulent J, Parkin DM, Ferlay J, Mathers C, et al. Global burden of cancer in 2008: a systematic analysis of disability-adjusted life-years in 12 world regions. Lancet 2012;380:1840-50.
3. Parkin DM. The global health burden of infection-associated cancers in the year 2002. Int J Cancer 2006;118:3030-44.
4. Makarova-Rusher OV, Altekruse SF, McNeel TS, Ulahannan S, Duffy AG, et al. Population attributable fractions of risk factors for hepatocellular carcinoma in the United States. Cancer 2016;122:1757-65.
5. Fattovich G, Stroffolini T, Zagni I, Donato F. Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology 2004;127:S35-50.
6. Kanwal F, Hoang T, Kramer JR, Asch SM, Goetz MB, et al. Increasing prevalence of HCC and cirrhosis in patients with chronic hepatitis C virus infection. Gastroenterology 2011;140:1182-8.
8. Zhang BH, Yang BH, Tang ZY. Randomized controlled trial of screening for hepatocellular carcinoma. J Cancer Res Clin Oncol 2004;130:417-22.
9. Chaiteerakij R, Zhang X, Addissie BD, Mohamed EA, Harmsen WS, et al. Combinations of biomarkers and Milan criteria for predicting hepatocellular carcinoma recurrence after liver transplantation. Liver Transpl 2015;21:559-606.
10. Zhu AX, Finn RS, Edeline J, Cattan S, Ogasawara S, et al. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial. Lancet Oncol 2018;19:940-52.
11. Umeda S, Kanda M, Kodera Y. Emerging evidence of molecular biomarkers in hepatocellular carcinoma. Histol Histopathol 2018;33:343-55.
12. Khan FS, Ali I, Afridi UK, Ishtiaq M, Mehmood R. Epigenetic mechanisms regulating the development of hepatocellular carcinoma and their promise for therapeutics. Hepatol Int 2017;11:45-53.
13. Di Costanzo A, Del Gaudio N, Migliaccio A, Altucci L. Epigenetic drugs against cancer: an evolving landscape. Arch Toxicol 2014;88:1651-68.
14. Dhanak D, Jackson P. Development and classes of epigenetic drugs for cancer. Biochem Biophys Res Commun 2014;455:58-69.
15. Pathil A, Armeanu S, Venturelli S, Mascagni P, Weiss TS, et al. HDAC inhibitor treatment of hepatoma cells induces both TRAIL-independent apoptosis and restoration of sensitivity to TRAIL. Hepatology 2006;43:425-34.
16. Yeo W, Chung HC, Chan SL, Wang LZ, Lim R, et al. Epigenetic therapy using belinostat for patients with unresectable hepatocellular carcinoma: a multicenter phase i/ii study with biomarker and pharmacokinetic analysis of tumors from patients in the Mayo Phase II Consortium and the Cancer Therapeutics Research Group. J Clin Oncol 2012;30:3361-7.
18. Peterson ML, Ma C, Spear BT. Zhx2 and Zbtb20: novel regulators of postnatal alpha-fetoprotein repression and their potential role in gene reactivation during liver cancer. Semin Cancer Biol 2011;21:21-7.
19. Grizzi F, Colombo P, Taverna G, Chiriva-Internati M, Cobos E, et al. Geometry of human vascular system: is it an obstacle for quantifying antiangiogenic therapies? Appl Immunohistochem Mol Morphol 2007;15:134-9.
20. Gonzalez SA. Novel biomarkers for hepatocellular carcinoma surveillance: has the future arrived? Hepatobiliary Surg Nutr 2014;3:410-4.
21. Schütte K, Schulz C, Link A, Malfertheiner P. Current biomarkers for hepatocellular carcinoma: surveillance, diagnosis and prediction of prognosis. World J Hepatol 2015;7:139-49.
22. Tsukuma H, Hiyama T, Tanaka S, Nakao M, Yabuuchi T, et al. Risk factors for hepatocellular carcinoma among patients with chronic liver disease. N Engl J Med 1993;328:1797-1801.
23. McMahon BJ, Bulkow L, Harpster A, Snowball M, Lanier A, et al. Screening for hepatocellular carcinoma in Alaska natives infected with chronic hepatitis B: a 16-year population-based study. Hepatology 2000;32:842-6.
24. Di Bisceglie AM, Sterling RK, Chung RT, Everhart JE, Dienstag JL, et al. Serum alpha-fetoprotein levels in patients with advanced hepatitis C: results from the HALT-C trial. J Hepatol 2005;43:434-41.
25. Bruix J, Sherman M; American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: an update. Hepatology 2011;53:1020-2.
26. Yamashita T, Budhu A, Forgues M, Wang XW. Activation of hepatic stem cell marker EpCAM by Wnt-beta-catenin signaling in hepatocellular carcinoma. Cancer Res 2007;67:10831-9.
27. Villanueva A, Minguez B, Forner A, Reig M, Llovet JM. Hepatocellular carcinoma: novel molecular approaches for diagnosis, prognosis, and therapy. Annu Rev Med 2010;61:317-28.
28. Hoshida Y, Nijman SM, Kobayashi M, Chan JA, Brunet JP, et al. Integrative transcriptome analysis reveals common molecular subclasses of human hepatocellular carcinoma. Cancer Res 2009;69:7385-92.
29. Tao LY, Cai L, He XD, Liu W, Qu Q. Comparison of serum tumor markers for intrahepatic cholangiocarcinoma and hepatocellular carcinoma. Am Surg 2010;76:1210-3.
30. Rimola J, Forner A, Reig M, Vilana R, de Lope CR, et al. Cholangiocarcinoma in cirrhosis: absence of contrast washout in delayed phases by magnetic resonance imaging avoids misdiagnosis of hepatocellular carcinoma. Hepatology 2009;50:791-8.
31. Cancer European Organisation For Research And Treatment Of; European Association For The Study Of The Liver. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 2012;56:908-43.
32. Heimbach JK, Kulik LM, Finn RS, Sirlin CB, Abecassis MM, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology 2018;67:358-80.
33. Singal AG, Pillai A, Tiro J. Early detection, curative treatment, and survival rates for hepatocellular carcinoma surveillance in patients with cirrhosis: a meta-analysis. PLoS Med 2014;11:e1001624.
34. Li C, Shen JY, Zhang XY, Peng W, Wen TF, et al. Predictors of futile liver resection for patients with Barcelona clinic liver cancer stage B/C hepatocellular carcinoma. J Gastrointest Surg 2018;22:496-502.
35. Mazzaferro V, Sposito C, Zhou J, Pinna AD, De Carlis L, et al. Metroticket 2.0 model for analysis of competing risks of death after liver transplantation for hepatocellular carcinoma. Gastroenterology 2018;154:128-39.
36. Sangiovanni A, Del Ninno E, Fasani P, De Fazio C, Ronchi G, et al. Increased survival of cirrhotic patients with a hepatocellular carcinoma detected during surveillance. Gastroenterology 2004;126:1005-14.
37. Pontisso P, Quarta S, Caberlotto C, Beneduce L, Marino M, et al. Progressive increase of SCCA-IgM immune complexes in cirrhotic patients is associated with development of hepatocellular carcinoma. Int J cancer 2006;119:735-40.
38. Kinoshita A, Onoda H, Fushiya N, Koike K, Nishino H, et al. Staging systems for hepatocellular carcinoma: current status and future perspectives. World J Hepatol 2015;7:406-24.
39. Liu L, Zhao Y, Jia J, Chen H, Bai W, et al. The prognostic value of alpha-fetoprotein response for advanced-stage hepatocellular carcinoma treated with sorafenib combined with transarterial chemoembolization. Sci Rep 2016;doi:10.
40. Personeni N, Bozzarelli S, Pressiani T, Rimassa L, Tronconi MC, et al. Usefulness of alpha-fetoprotein response in patients treated with sorafenib for advanced hepatocellular carcinoma. J Hepatol 2012;57:101-7.
41. Nakazawa T, Hidaka H, Takada J, Okuwaki Y, Tanaka Y, et al. Early increase in α-fetoprotein for predicting unfavorable clinical outcomes in patients with advanced hepatocellular carcinoma treated with sorafenib. Eur J Gastroenterol Hepatol 2013;25:683-9.
42. Tsuchiya N, Sawada Y, Endo I, Saito K, Uemura Y, et al. Biomarkers for the early diagnosis of hepatocellular carcinoma. World J Gastroenterol 2015;21:10573-83.
43. Marrero JA, Su GL, Wei W, Emick D, Conjeevaram HS, et al. Des-gamma carboxyprothrombin can differentiate hepatocellular carcinoma from nonmalignant chronic liver disease in American patients. Hepatology 2003;37:1114-21.
44. Kumada T, Toyoda H, Tada T, Kiriyama S, Tanikawa M, et al. High-sensitivity Lens culinaris agglutinin-reactive alpha-fetoprotein assay predicts early detection of hepatocellular carcinoma. J Gastroenterol 2014;49:555-63.
45. Koike Y, Shiratori Y, Sato S, Obi S, Teratani T, et al. Des-gamma-carboxy prothrombin as a useful predisposing factor for the development of portal venous invasion in patients with hepatocellular carcinoma: a prospective analysis of 227 patients. Cancer 2001;91:561-9.
46. Sterling RK, Jeffers L, Gordon F, Sherman M, Venook AP, et al. Clinical utility of AFP-L3% measurement in North American patients with HCV-related cirrhosis. Am J Gastroenterol 2007;102:2196-205.
47. Grizzi F, Franceschini B, Hamrick C, Frezza EE, Cobos E, et al. Usefulness of cancer-testis antigens as biomarkers for the diagnosis and treatment of hepatocellular carcinoma. J Transl Med 2007;5:3.
48. Zhang D, Liu Z, Yin X, Qi X, Lu B, et al. Prognostic value of PIVKA-II in hepatocellular carcinoma patients receiving curative ablation: a systematic review and meta-analysis. Int J Biol Markers 2018;33:266-74.
49. Marrero JA, Feng Z, Wang Y, Nguyen MH, Befeler AS, Roberts LR, Reddy KR, Harnois D, Llovet JM, Normolle D, Dalhgren J, Chia D, Lok AS, Wagner PD, Srivastava S, Schwartz M. Alpha-fetoprotein, des-gamma carboxyprothrombin, and lectin-bound alpha-fetoprotein in early hepatocellular carcinoma. Gastroenterology 2009;137:110-8.
50. Lok AS, Sterling RK, Everhart JE, Wright EC, Hoefs JC, et al. Des-gamma-carboxy prothrombin and alpha-fetoprotein as biomarkers for the early detection of hepatocellular carcinoma. Gastroenterology 2010;138:493-502.
51. Liu Z, Ma Y, Yang J, Qin H. Upregulated and downregulated proteins in hepatocellular carcinoma: a systematic review of proteomic profiling studies. OMICS 2011;15:61-71.
52. Budhu A, Roessler S, Zhao X, Yu Z, Forgues M, et al. Integrated metabolite and gene expression profiles identify lipid biomarkers associated with progression of hepatocellular carcinoma and patient outcomes. Gastroenterology 2013;144:1066-75.
53. Beyoğlu D, Imbeaud S, Maurhofer O, Bioulac-Sage P, Zucman-Rossi J, et al. Tissue metabolomics of hepatocellular carcinoma: tumor energy metabolism and the role of transcriptomic classification. Hepatology 2013;58:229-38.
54. Fitian AI, Nelson DR, Liu C, Xu Y, Ararat M, et al. Integrated metabolomic profiling of hepatocellular carcinoma in hepatitis C cirrhosis through GC/MS and UPLC/MS-MS. Liver Int 2014;34:1428-44.
55. Ruhaak LR, Miyamoto S, Lebrilla CB. Developments in the identification of glycan biomarkers for the detection of cancer. Mol Cell Proteomics 2013;12:846-55.
56. Chen K, Shi W, Xin Z, Wang H, Zhu X, et al. Replication of genome wide association studies on hepatocellular carcinoma susceptibility loci in a chinese population. PLoS One 2013; doi: 10.1371/journal.pone.0077315.
57. Hippo Y, Watanabe K, Watanabe A, Midorikawa Y, Yamamoto S, et al. Identification of soluble NH2-terminal fragment of glypican-3 as a serological marker for early-stage hepatocellular carcinoma. Cancer Res 2004;64:2418-23.
58. Xu C, Yan Z, Zhou L, Wang Y. A comparison of glypican-3 with alpha-fetoprotein as a serum marker for hepatocellular carcinoma: a meta-analysis. J Cancer Res Clin Oncol 2013;139:1417-24.
59. Tomimaru Y, Eguchi H, Nagano H, Wada H, Kobayashi S, et al. Circulating microRNA-21 as a novel biomarker for hepatocellular carcinoma. J Hepatol 2012;56:167-75.
60. Chuma M, Sakamoto M, Yamazaki K, Ohta T, Ohki M, et al. Expression profiling in multistage hepatocarcinogenesis: identification of HSP70 as a molecular marker of early hepatocellular carcinoma. Hepatology 2003;37:198-207.
61. Osada T, Sakamoto M, Nagawa H, Yamamoto J, Matsuno Y, et al. Acquisition of glutamine synthetase expression in human hepatocarcinogenesis: relation to disease recurrence and possible regulation by ubiquitin-dependent proteolysis. Cancer 1999;85:819-31.
62. Feng J, Zhu R, Chang C, Yu L, Cao F, et al. CK19 and glypican 3 expression profiling in the prognostic indication for patients with HCC after surgical resection. PLoS One 2016; doi: 10.1371/journal.pone.0151501.
63. Sun DW, Zhang YY, Sun XD, Chen YG, Qiu W, et al. Prognostic value of cytokeratin 19 in hepatocellular carcinoma: a meta-analysis. Clin Chim Acta 2015;448:161-9.
64. Lee JI, Lee JW, Kim JM, Kim JK, Chung HJ, et al. Prognosis of hepatocellular carcinoma expressing cytokeratin 19: comparison with other liver cancers. World J Gastroenterol 2012;18:4751-7.
65. Marrero JA, Romano PR, Nikolaeva O, Steel L, Mehta A, et al. GP73, a resident Golgi glycoprotein, is a novel serum marker for hepatocellular carcinoma. J Hepatol 2005;43:1007-12.
66. Tian L, Wang Y, Xu D, Gui J, Jia X, et al. Serological AFP/Golgi protein 73 could be a new diagnostic parameter of hepatic diseases. Int J Cancer 2011;129:1923-31.
67. Xu WJ, Guo BL, Han YG, Shi L, Ma WS. Diagnostic value of alpha-fetoprotein-L3 and Golgi protein 73 in hepatocellular carcinomas with low AFP levels. Tumor Biol 2014;35:12069-74.
68. Qin L. Osteopontin is a promoter for hepatocellular carcinoma metastasis: a summary of 10 years of studies. Front Med 2014;8:24-32.
69. Ramchandani D, Weber GF. Interactions between osteopontin and vascular endothelial growth factor: implications for cancer. Biochim Biophys Acta 2015;1855:202-22.
70. Shang S, Plymoth A, Ge S, Feng Z, Rosen HR, et al. Identification of osteopontin as a novel marker for early hepatocellular carcinoma. Hepatology 2012;55:483-90.
71. Weber GF. The cancer biomarker osteopontin: combination with other markers. Cancer Genomics and Proteomics 2011;8:263-88.
72. Giannelli G, Marinosci F, Sgarra C, Lupo L, Dentico P, et al. Clinical role of tissue and serum levels of SCCA antigen in hepatocellular carcinoma. Int J Cancer 2005;116:579-83.
73. Pozzan C, Cardin R, Piciocchi M, Cazzagon N, Maddalo G, et al. Diagnostic and prognostic role of SCCA-IgM serum levels in hepatocellular carcinoma (HCC). J Gastroenterol Hepatol 2014;29:1637-44.
74. Lokman NA, Ween MP, Oehler MK, Ricciardelli C. The role of annexin A2 in tumorigenesis and cancer progression. Cancer Microenviron 2011;4:199-208.
75. Sun Y, Gao G, Cai J, Wang Y, Qu X, et al. Annexin A2 is a discriminative serological candidate in early hepatocellular carcinoma. Carcinogenesis 2013;34:595-604.
76. Fu LL, Wen X, Bao JK, Liu B. MicroRNA-modulated autophagic signaling networks in cancer. Int J Biochem Cell Biol 2012;44:733-6.
78. Borel F, Konstantinova P, Jansen PL. Diagnostic and therapeutic potential of miRNA signatures in patients with hepatocellular carcinoma. J Hepatol 2012;56:1371-83.
79. Chen X, Zhang Q, Ma W, Lan T, Hong Z, et al. The abnormal expression of microRNA-542-3p in hepatocellular carcinoma and its clinical significance. Dis Markers 2018; doi: 10.1155/2018/3973250.
80. Wong CC, Wong CM, Tung EK, Au SL, Lee JM, et al. The microRNA miR-139 suppresses metastasis and progression of hepatocellular carcinoma by down-regulating rho-kinase 2. Gastroenterology 2011;140:322-31.
81. Sato F, Hatano E, Kitamura K, Myomoto A, Fujiwara T, et al. MicroRNA profile predicts recurrence after resection in patients with hepatocellular carcinoma within the Milan criteria. PLoS One 2011; doi: 10.1371/journal.pone.0016435.
82. Mei Y, You Y, Xia J, Gong JP, Wang YB. Identifying differentially expressed microRNAs between cirrhotic and non-cirrhotic hepatocellular carcinoma and exploring their functions using bioinformatic analysis. Cell Physiol Biochem 2018;48:1443-56.
83. Wang H, Liang L, Dong Q, Huan L, He J, et al. Long noncoding RNA miR503HG, a prognostic indicator, inhibits tumor metastasis by regulating the HNRNPA2B1/NF-κB pathway in hepatocellular carcinoma. Theranostics 2018;8:2814-29.
84. Carninci P, Kasukawa T, Katayama S, Gough J, Frith MC, et al. The transcriptional landscape of the mammalian genome. Science 2005;309:1559-63.
85. Sun J, Bie B, Zhang S, Yang J, Li Z. Long non-coding RNAs: critical players in hepatocellular carcinoma. Int J Mol Sci 2014;15:20434-48.
86. Zhu X, Wu YB, Zhou J, Kang DM. Upregulation of lncRNA MEG3 promotes hepatic insulin resistance via increasing FoxO1 expression. Biochem Biophys Res Commun 2016;469:319-25.
87. Xu H, Dong X, Chen Y, Wang X. Serum exosomal hnRNPH1 mRNA as a novel marker for hepatocellular carcinoma. Clin Chem Lab Med 2018;56:479-84.
88. Zhang J, Zhang D, Zhao Q, Qi J, Li X, et al. A distinctively expressed long noncoding RNA, RP11-466I1.1, may serve as a prognostic biomarker in hepatocellular carcinoma. . Cancer Med 2018; doi: 10.1002/cam4.1565.
89. Imamura H, Matsuyama Y, Tanaka E, Ohkubo T, Hasegawa K, et al. Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy. J Hepatol 2003;38:200-7.
90. Xu W, Cao L, Chen L, Li J, Zhang XF, et al. Isolation of circulating tumor cells in patients with hepatocellular carcinoma using a novel cell separation strategy. Clin Cancer Res 2011;17:3783-93.
91. Fan JL, Yang YF, Yuan CH, Chen H, Wang FB. Circulating tumor cells for predicting the prognostic of patients with hepatocellular carcinoma: a meta analysis. Cell Physiol Biochem 2015;37:629-40.
92. Sun C, Liao W, Deng Z, Li E, Feng Q, et al. The diagnostic value of assays for circulating tumor cells in hepatocellular carcinoma: a meta-analysis. Medicine (Baltimore) 2017; doi: 10.1097/MD.0000000000007513.
93. Leon SA, Shapiro B, Sklaroff DM, Yaros MJ. Free DNA in the serum of cancer patients and the effect of therapy. Cancer Res 1977;37:646-50.
94. Swystun LL, Mukherjee S, Liaw PC. Breast cancer chemotherapy induces the release of cell-free dna, a novel procoagulant stimulus. J Thromb Haemost 2011;9:2313-21.
95. García-Olmo DC, Domínguez C, García-Arranz M, Anker P, Stroun M, et al. Cell-free nucleic acids circulating in the plasma of colorectal cancer patients induce the oncogenic transformation of susceptible cultured cells. Cancer Res 2010;70:560-7.
96. Kirk GD, Lesi OA, Mendy M, Szyma-ska K, Whittle H, et al. 249(ser) TP53 mutation in plasma DNA, hepatitis B viral infection, and risk of hepatocellular carcinoma. Oncogene 2005;24:5858-67.
97. Liao W, Mao Y, Ge P, Yang H, Xu H, et al. Value of quantitative and qualitative analyses of circulating cell-free DNA as diagnostic tools for hepatocellular carcinoma: a meta-analysis. Medicine (Baltimore) 2015; doi: 10.1097/MD.0000000000000722.
98. Shi M, Chen MS, Sekar K, Tan CK, Ooi LL, et al. A blood-based three-gene signature for the non-invasive detection of early human hepatocellular carcinoma. Eur J Cancer 2014;50:928-36.
99. Hann HW, Jain S, Park G, Steffen JD, Song W, et al. Detection of urine DNA markers for monitoring recurrent hepatocellular carcinoma. Hepatoma Res 2017;3:105-11.
100. Luo P, Yin P, Hua R, Tan Y, Li Z, et al. A large-scale, multicenter serum metabolite biomarker identification study for the early detection of hepatocellular carcinoma. Hepatology 2017; doi: 10.1002/hep.29561.
101. Yin H, Tan Z, Wu J, Zhu J, Shedden KA, et al. Mass-selected site-specific core-fucosylation of serum proteins in hepatocellular carcinoma. J Proteome Res 2015;14:4876-84.
102. Gray J, Chattopadhyay D, Beale GS, Patman GL, Miele L, et al. A proteomic strategy to identify novel serum biomarkers for liver cirrhosis and hepatocellular cancer in individuals with fatty liver disease. BMC Cancer 2009;9:271.
103. Zinkin NT, Grall F, Bhaskar K, Otu HH, Spentzos D, et al. Serum proteomics and biomarkers in hepatocellular carcinoma and chronic liver disease. Clin Cancer Res 2008;14:470-7.
104. Nahon P, Zucman-Rossi J. Single nucleotide polymorphisms and risk of hepatocellular carcinoma in cirrhosis. J Hepatol 2012;57:663-74.
105. Walker AJ, Peacock CJ, Pedergnana V, STOP-HCV Consortium STOP, Irving WL. Host genetic factors associated with hepatocellular carcinoma in patients with hepatitis C virus infection: a systematic review. J Viral Hepat 2018;25:442-56.
106. Hoshida Y, Villanueva A, Sangiovanni A, Sole M, Hur C, et al. Prognostic gene-expression signature for patients with hepatitis C-related early-stage cirrhosis. Gastroenterology 2013;144:1024-30.
107. Llovet JM, Zucman-Rossi J, Pikarsky E, Sangro B, Schwartz M, et al. Hepatocellular carcinoma. Nat Rev Dis Primers 2016;2:16018.
108. Llovet JM, Chen Y, Wurmbach E, Roayaie S, Fiel MI, et al. A molecular signature to discriminate dysplastic nodules from early hepatocellular carcinoma in HCV cirrhosis. Gastroenterology 2006;131:1758-67.
109. Han X, Wang J, Sun Y. Circulating tumor DNA as biomarkers for cancer detection. Genomics Proteomics Bioinformatics 2017;15:59-72.
110. Cabel L, Proudhon C, Buecher B, Pierga JY, Bidard FC. Circulating tumor DNA detection in hepatocellular carcinoma. Ann Oncol 2018;29:1094-6.
111. Nault JC, De Reyniès A, Villanueva A, Calderaro J, Rebouissou S, et al. A hepatocellular carcinoma 5-gene score associated with survival of patients after liver resection. Gastroenterology 2013;145:176-87.
112. Villa E, Critelli R, Lei B, Marzocchi G, Cammà C, et al. Neoangiogenesis-related genes are hallmarks of fast-growing hepatocellular carcinomas and worst survival. Results from a prospective study. . Gut 2016;65:861-9.
113. Hoshida Y, Villanueva A, Kobayashi M, Peix J, Chiang DY, et al. Gene expression in fixed tissues and outcome in hepatocellular carcinoma. N Engl J Med 2008;359:1995-2004.
114. Arao T, Ueshima K, Matsumoto K, Nagai T, Kimura H, et al. FGF3/FGF4 amplification and multiple lung metastases in responders to sorafenib in hepatocellular carcinoma. Hepatology 2013;57:1407-15.
115. Bruix J, Cheng AL, Meinhardt G, Nakajima K, De Sanctis Y, et al. Prognostic factors and predictors of sorafenib benefit in patients with hepatocellular carcinoma: analysis of two phase III studies. J Hepatol 2017;67:999-1008.
116. Llovet JM, Villanueva A, Lachenmayer A, Finn RS. Advances in targeted therapies for hepatocellular carcinoma in the genomic era. Nat Rev Clin Oncol 2015;12:408-24.
117. Llovet JM, Pe-a CE, Lathia CD, Shan M, Meinhardt G, et al. Plasma biomarkers as predictors of outcome in patients with advanced hepatocellular carcinoma. Clin Cancer Res 2012;18:2290-300.
118. Bruix J, Qin S, Merle P, Granito A, Huang YH, et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2017;389:56-66.
119. Kudo M, Finn RS, Qin S, Han KH, Ikeda K, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet 2018;391:1163-73.
120. Abou-Alfa GK, Meyer T, Cheng AL, El-Khoueiry AB, Rimassa L, et al. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. N Engl J Med 2018;379:54-63.
121. Zhu AX, Kang YK, Yen CJ, Finn RS, Galle PR, et al. REACH-2: a randomized, double-blind, placebo-controlled phase 3 study of ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma (HCC) and elevated baseline alpha-fetoprotein (AFP) following first-line sorafe. J Clin Oncol 2018;36:4003.
122. El-Khoueiry AB, Sangro B, Yau T, Crocenzi TS, Kudo M, et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet 2017;389:2492-502.
123. Maleki Vareki S, Garrigós C, Duran I. Biomarkers of response to PD-1/PD-L1 inhibition. Crit Rev Oncol Hematol 2017;116:116-24.
124. Sia D, Jiao Y, Martinez-Quetglas I, Kuchuk O, Villacorta-Martin C, et al. Identification of an immune-specific class of hepatocellular carcinoma, based on molecular features. Gastroenterology 2017;153:812-26.
125. Wang L, Yao M, Pan LH, Qian Q, Yao DF. Glypican-3 is a biomarker and a therapeutic target of hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int 2015;14:361-6.
126. Filmus J, Capurro M. Glypican-3: a marker and a therapeutic target in hepatocellular carcinoma. FEBS J 2013;280:2471-6.
127. Fu X, Zhu Y, Zheng B, Zou Y, Wang C, et al. KIFC1, a novel potential prognostic factor and therapeutic target in hepatocellular carcinoma. Int J Oncol 2018; doi: 10.3892/ijo.2018.4348.
128. Hann HW, Wan S, Lai Y, Hann RS, Myers RE, et al. Aspartate aminotransferase to platelet ratio index as a prospective predictor of hepatocellular carcinoma risk in patients with chronic hepatitis B virus infection. J Gastroenterol Hepatol 2015;30:131-8.
129. Tang T, Qiu JL, Li GW, Huang MP, Li Y, et al. Aspartate aminotransferase-to-platelet ratio predicts response to transarterial chemoembolisation and prognosis in hepatocellular carcinoma patients. Clin Radiol 2018;73:259-65.
130. Suh B, Park S, Shin DW, Yun JM, Yang HK, et al. High liver fibrosis index FIB-4 is highly predictive of hepatocellular carcinoma in chronic hepatitis B carriers. Hepatology 2015;61:1261-8.
131. Demir M, Grünewald F, Lang S, Schramm C, Bowe A, et al. Elevated liver fibrosis index FIB-4 is not reliable for HCC risk stratification in predominantly non-Asian CHB patients. Medicine (Baltimore) 2016; doi: 10.1097/MD.0000000000004602.
132. Toyoda H, Tada T, Tachi Y, Hirai T, Yasuda S, et al. Liver fibrosis indices for identifying patients at low risk of developing hepatocellular carcinoma after eradication of HCV. Antivir Ther 2017;22:185-93.
