REFERENCES
1. Organization World Health. Globocan 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. Available from: http://globocan.iarc.fr/Default.aspx. [Last accessed on 27 Jun].
2. Malvezzi M, Bertuccio P, Levi F, La Vecchia C, Negri E. European cancer mortality predictions for the year 2012. Ann Oncol 2012;23:1044-52.
3. Ronot M, Bouattour M, Wassermann J, Bruno O, Dreyer C, Larroque B, Castera L, Vilgrain V, Belghiti J, Raymond E, Faivre S. Alternative Response Criteria (Choi, European Association for the Study of the Liver, and Modified Response Evaluation Criteria in Solid Tumors [RECIST]) versus RECIST 1.1 in patients with advanced hepatocellular carcinoma treated with sorafenib. Oncologist 2014;19:394-402.
4. Sterling RK, Jeffers L, Gordon F, Venook AP, Reddy KR, Satomura S, Kanke F, Schwartz ME, Sherman M. Utility of lens culinaris agglutinin-reactive fraction of α-fetoprotein and des-gamma-carboxy prothrombin, alone or in combination, as biomarkers for hepatocellular carcinoma. Clin Gastroenterol Hepatol 2009;7:104-13.
5. Debruyne EN, Delanghe JR. Diagnosing and monitoring hepatocellular carcinoma with alpha-fetoprotein: new aspects and applications. Clin Chim Acta 2008;395:19-26.
6. Zhang BH, Yang BH, Tang ZY. Randomized controlled trial of screening for hepatocellular carcinoma. J Cancer Res Clin Oncol 2004;130:417-22.
7. Chayvialle JAP, Ganguli PC. Radioimmunoassay of alpha-fetoprotein in human plasma. Lancet 1973;301:1355-7.
8. Lok AS, Sterling RK, Everhart JE, Wright EC, Hoefs JC, Di Bisceglie AM, Morgan TR, Kim HY, Lee WM, Bonkovsky HL, Dienstag JL. Des-γ-carboxy prothrombin and α-fetoprotein as biomarkers for the early detection of hepatocellular carcinoma. Gastroenterology 2010;138:493-502.
9. 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. α-fetoprotein, des-γ carboxyprothrombin, and lectin-bound α-fetoprotein in early hepatocellular carcinoma. Gastroenterology 2009;137:110-8.
10. Heimbach JK, Kulik LM, Finn RS, Sirlin CB, Abecassis MM, Roberts LR, Zhu AX, Murad MH, Marrero JA. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology 2018;67:358-80.
11. Llovet JM, Ducreux M, Lencioni R, Di Bisceglie AM, Galle PR, Dufour JF, Greten TF, Raymond E, Roskams T, De Baere T, Ducreux M, Mazzaferro V, Bernardi M, Bruix J, Colombo M, Zhu A. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 2012;56:908-43.
12. 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.
13. She WH, Chan ACY, Cheung TT, Lo CM, Chok KSH. Survival outcomes of liver transplantation for hepatocellular carcinoma in patients with normal, high and very high preoperative alpha-fetoprotein levels. World J Hepatol 2018;10:308-18.
14. Toyoda H, Kumada T, Kiriyama S, Sone Y, Tanikawa M, Hisanaga Y, Hayashi K, Honda T, Kitabatake S, Kuzuya T, Nonogaki K, Kasugai T, Shimizu J. Changes in the characteristics and survival rate of hepatocellular carcinoma from 1976 to 2000: analysis of 1365 patients in a single institution in Japan. Cancer 2004;100:2415-21.
15. Tsuchiya N, Sawada Y, Endo I, Saito K, Uemura Y, Nakatsura T. Biomarkers for the early diagnosis of hepatocellular carcinoma. World J Gastroenterol 2015;21:10573-83.
16. Spangenberg HC, Thimme R, Blum HE. Serum markers of hepatocellular carcinoma. Semin Liver Dis 2006;26:385-90.
17. Li D, Mallory T, Satomura S. AFP-L3: a new generation of tumor marker for hepatocellular carcinoma. Clin Chim Acta 2001;313:15-9.
18. Abdel-Aziz MM, Elshal MF, Abass AT, El-Kafrawy S, Ezzat S, Abdel-Wahab M. Comparison of AFP-L3 and p53 antigen concentration with alpha-fetoprotein as serum markers for hepatocellular carcinoma. Clin Lab 2016;62:1121-9.
19. Oda K, Ido A, Tamai T, Matsushita M, Kumagai K, Mawatari SI, Saishoji A, Kure T, Ohno K, Toyokura E, Imanaka D, Moriuchi A, Uto H, Oketani M, Hashiguchi T, Tsubouchi H. Highly sensitive lens culinaris agglutinin-reactive α-fetoprotein is useful for early detection of hepatocellular carcinoma in patients with chronic liver disease. Oncol Rep 2011;26:1227-33.
20. Yi X, Yu S, Bao Y. Alpha-fetoprotein-L3 in hepatocellular carcinoma: a meta-analysis. Clin Chim Acta 2013;425:212-20.
21. Bertino G, Ardiri AM, Boemi PM, Ierna D, Interlandi D, Caruso L, Minona E, Trovato MA, Vicari S, Li Destri G, Puleo S. A study about mechanisms of des-gamma-carboxy prothrombin's production in hepatocellular carcinoma. Panminerva Med 2008;50:221-6.
22. Okuda H, Nakanishi T, Takatsu K, Saito A, Hayashi N, Yamamoto M, Takasaki K, Nakano M. Comparison of clinicopathological features of patients with hepatocellular carcinoma seropositive for α-fetoprotein alone and those seropositive for des-γ-carboxy prothrombin alone. Gastroenterol Hepatol 2001;16:1290-6.
23. Hong YM, Cho M, Yoon KT, Chu CW, Yang KH, Park YM, Rhu JH. Risk factors of early recurrence after curative hepatectomy in hepatocellular carcinoma. Tumor Biol 2017;39:1-9.
24. Hamamura K, Shiratori Y, Shiina S, Imamura M, Obi S, Sato S, Yoshida H, Omata M. Unique clinical characteristics of patients with hepatocellular carcinoma who present with high plasma des-gamma-carboxy prothrombin and low serum alpha-fetoprotein. Cancer 2000;88:1557-64.
25. Bertino G, Ardiri AM, Calvagno GS, Bertino N, Boemi PM. Prognostic and diagnostic value of des-γ-carboxy prothrombin in liver cancer. Drug News Perspect 2010;23:498-508.
26. Suehiro T, Matsumata T, Itasaka H, Taketomi A, Yamamoto K, Sugimachi K. Des-gamma-carboxy prothrombin and proliferative activity of hepatocellular carcinoma. Surgery 1995;117:682-91.
27. Sung YK, Hwang SY, Park MK, Farooq M, Han IS, Bae HI, Kim JC, Kim M. Glypican-3 is overexpressed in human hepatocellular carcinoma. Cancer Sci 2003;94:259-62.
28. Liu XF, Hu De Z, Liu XC, Cao Y, Ding CM, Hu CJ. Diagnostic accuracy of serum glypican-3 for hepatocellular carcinoma: a systematic review and meta-analysis. Clin Biochem 2014;47:196-200.
29. Tahon AM, El-Ghanam MZ, Zaky S, Emran TM, Bersy AM, El-Raey F, E AZ, El Kharsawy AM, Johar D. Significance of glypican-3 in early detection of hepatocellular carcinoma in cirrhotic patients. J Gastrointest Cancer 2018; doi: 10.1007/s12029-018-0095-2.
30. El-Saadany S, El-Demerdash T, Helmy A, Mayah WW, El-Sayed Hussein B, Hassanien M, Elmashad N, Fouad MA, Basha EA. Diagnostic value of glypican-3 for hepatocellular carcinomas. Asian Pac J Cancer Prev 2018;19:811-7.
31. Libbrecht L, Severi T, Cassiman D, Borght Vander S, Pirenne J, Nevens F, Verslype C, ven Pelt J, Roskams T. Glypican-3 expression distinguishes small hepatocellular carcinomas from cirrhosis, dysplastic nodules, and focal nodular hyperplasia-like nodules. Am J Surg Pathol 2006;30:1405-11.
32. Capurro MI, Xiang YY, Lobe C, Filmus J. Glypican-3 promotes the growth of hepatocellular carcinoma by stimulating canonical Wnt signaling. Cancer Res 2005;65:6245-54.
33. Filmus J, Capurro M. Glypican-3: a marker and a therapeutic target in hepatocellular carcinoma. FEBS J 2013;280:2471-6.
34. Abou-Alfa GK, Yen CJ, Hsu CH, O'Donoghue J, Beylergil V, Ruan S, Pandit-Taskar N, Gansukh B, Lyashchenko SK, Ma J, Wan P, Shao YY, Lin ZZ, Frenette C, O'Neil B, Schwartz L, Smith-Jones PM, Ohtomo T, Tanaka T, Morikawa H, Maki Y, Ohishi N, Chen YC, Agajano CJ. Phase Ib study of codrituzumab in combination with sorafenib in patients with non-curable advanced hepatocellular carcinoma (HCC). Cancer Chemother Pharmacol 2017;79:421-9.
35. Ikeda M, Ohkawa S, Okusaka T, Mitsunaga S, Kobayashi S, Morizane C, Suzuki I, Yamamoto S, Furuse J. Japanese phase I study of GC33, a humanized antibody against glypican-3 for advanced hepatocellular carcinoma. Cancer Sci 2014;105:455-62.
36. Abou-Alfa GK, Puig O, Daniele B, Kudo M, Merle P, Park JW, Ross P, Peron JM, Ebert O, Chan S, Poon TP, Colombo M, Okusaka T, Ryoo BY, Minguez B, Tanaka T, Ohtomo T, Ukrainskyj S, Boisserie F, Rutman O, Chen YC, Xu C, Shochat E, Jukofsky L, Reis B, Chen G, Di Laurenzio L, Lee R, Yen CJ. Randomized phase II placebo controlled study of codrituzumab in previously treated patients with advanced hepatocellular carcinoma. J Hepatol 2016;65:289-95.
37. Wu Q, Pi L, Le Trinh T, Zuo C, Xia M, Jiao Y, Hou Z, Jo S, Puszyk W, Pham K, Nelson DR, Robertson K, Ostrov D, Rameshwar P, Xia CQ, Liu C. A novel vaccine targeting glypican-3 as a treatment for hepatocellular carcinoma. Mol Ther 2017;25:2299-308.
38. Sawada Y, Yoshikawa T, Nobuoka D, Shirakawa H, Kuronuma T, Motomura Y, Mizuno S, Ishii H, Nakachi K, Konishi M, Nakagohri T, Takahashi S, Gotohda N, Takayama T, Yamao K, Uesaka K, Furuse J, Kinoshita T, Nakatsura T. Phase I trial of a glypican-3-derived peptide vaccine for advanced hepatocellular carcinoma: immunologic evidence and potential for improving overall survival. Clin Cancer Res 2012;18:3686-96.
39. Tsuchiya N, Yoshikawa T, Fujinami N, Saito K, Mizuno S, Sawada Y, Endo I, Nakatsura T. Immunological efficacy of glypican-3 peptide vaccine in patients with advanced hepatocellular carcinoma. Oncoimmunology 2017;6:e1346764.
40. Sun Y, Sheshadri N, Zong WX. SERPINB3 and B4: from biochemistry to biology. Semin Cell Dev Biol 2017;62:170-7.
41. Pontisso P, Calabrese F, Benvegnù L, Lise M, Belluco C, Ruvoletto MG, De Falco S, Marino M, Valente M, Nitti D, Gatta A, Fassina G. Overexpression of squamous cell carcinoma antigen variants in hepatocellular carcinoma. Br J Cancer 2004;90:833-7.
42. Turato C, Cannito S, Simonato D, Villano G, Morello E, Terrin L, Quarta S, Biasiolo A, Ruvoletto M, Martini A, Fasolato S, Zanus G, Cillo U, Gatta A, Parola M, Pontisso P. SerpinB3 and Yap interplay increases Myc oncogenic activity. Sci Rep 2015;5:17701.
44. Biasiolo A, Trotta E, Fasolato S, Ruvoletto M, Martini A, Gallotta A, Fassina G, Angeli P, Gatta A, Pontisso P. Squamous cell carcinoma antigen-IgM is associated with hepatocellular carcinoma in patients with cirrhosis: a prospective study. Dig Liver Dis 2016;48:197-202.
45. Suminami Y, Nagashima S, Murakami A, Nawata S, Gondo T, Hirakawa H, Numa F, Silverman GA, Kato H. Suppression of a squamous cell carcinoma (scc)-related serpin, scc antigen, inhibits tumor growth with increased intratumor infiltration of natural killer cells. Cancer Res 2001;61:1776-80.
46. Martini A, Gallotta A, Pontisso P, Fassina G. Clinical applications of squamous cell carcinoma antigen-immunoglobulins M to monitor chronic hepatitis C. World J Hepatol 2015;7:2913-9.
47. Novo E, Villano G, Turato C, Cannito S, Paternostro C, Busletta C, Biasiolo A, Quarta S, Morello E, Bocca C, Miglietta A, David E, Sutti S, Plebani M, Albano E, Parola M, Pontisso P. SerpinB3 promotes pro-fibrogenic responses in activated hepatic stellate cells. Sci Rep 2017;7:3420.
48. Pozzan C, Cardin R, Piciocchi M, Cazzagon N, Maddalo G, Vanin V, Giacomin A, Pontisso P, Cillo U, Farinati F. Diagnostic and prognostic role of SCCA-IgM serum levels in hepatocellular carcinoma (HCC). J Gastroenterol Hepatol 2014;29:1637-44.
49. Heitzer E, Perakis S, Geigl JB, Speicher MR. The potential of liquid biopsies for the early detection of cancer. NPJ Precis Oncol 2017;1:36.
50. Crowley E, Di Nicolantonio F, Loupakis F, Bardelli A. Liquid biopsy: monitoring cancer-genetics in the blood. Nat Rev Clin Oncol 2013;10:472-84.
52. Alix-Panabières C, Pantel K. Clinical applications of circulating tumor cells and circulating tumor DNA as liquid biopsy. Cancer Discov 2016;6:479-91.
53. Okajima W, Komatsu S, Ichikawa D, Miyamae M, Ohashi T, Imamura T, Kiuchi J, Nishibeppu K, Arita T, Konishi H, Shiozaki A, Morimura R, Ikoma H, Okamoto K, Otsuji E. Liquid biopsy in patients with hepatocellular carcinoma: circulating tumor cells and cell-free nucleic acids. World J Gastroenterol 2017;23:5650-68.
54. Yin CQ, Yuan CH, Qu Z, Guan Q, Chen H, Wang FB. Liquid biopsy of hepatocellular carcinoma: circulating tumor-derived biomarkers. Dis Markers 2016;2016:1427849.
55. Zhou J, Huang A, Yang XR. Liquid biopsy and its potential for management of hepatocellular carcinoma. J Gastrointest Cancer 2016;47:157-67.
56. Labgaa I, Villanueva A. Liquid biopsy in liver cancer. Discov Med 2015;105:263-73.
58. Jiang Y, Wang D. Liquid biopsy in the OMICS era of tumor medicine. Open Access J Biomed Eng Appl 2018;1:115.
59. Ashworth T. A case of cancer in which cells similar to those in the tumours were seen in the blood after death. Aust Med J 1869;14:146-9.
60. Miller MC, Doyle GV, Terstappen LW. Significance of circulating tumor cells detected by the CellSearch system in patients with metastatic breast colorectal and prostate cancer. J Oncol 2010;2010:1-8.
61. Vona G, Estepa L, Béroud C, Damotte D, Capron F, Nalpas B, Mineur A, Franco D, Lacour B, Pol S, Bréchot C, Paterlini-Bréchot P. Impact of cytomorphological detection of circulating tumor cells in patients with liver cancer. Hepatology 2004;39:792-7.
62. Krebs MG, Metcalf RL, Carter L, Brady G, Blackhall FH, Dive C. Molecular analysis of circulating tumour cells - biology and biomarkers. Nat Rev Clin Oncol 2014;11:129-44.
63. Wu LJ, Pan Da Y, Pei XY, Chen H, Nguyen S, Kashyap A, Liu J, Wu J. Capturing circulating tumor cells of hepatocellular carcinoma. Cancer Lett 2012;326:17-22.
65. Guo W, Yang XR, Sun YF, Shen MN, Ma XL, Wu J, Zhang CY, Zhou Y, Xu Y, Hu B, Zhang X, Zhou J, Fan J. Clinical significance of EpCAM mRNA-positive circulating tumor cells in hepatocellular carcinoma by an optimized negative enrichment and qRT-PCR-based platform. Clin Cancer Res 2014;20:4794-805.
66. Nagrath S, Sequist V L, Maheswaran S, Bell DW, Irimia D, Ulkus L, Smith MR, Kwak EL, Digumarthy S, Muzikansky A, Ryan P, Balis UJ, Tompkins RG, Haber DA. Toner MIsolation of rare circulating tumour cells in cancer patients by microchip technology. Nature 2007;450:1235-9.
67. Xu W, Cao L, Chen L, Li J, Zhang XF, Qian HH, Kang XY, Zhang Y, Liao J, Shi LH, Yang YF, Wu MC, Yin ZF. Isolation of circulating tumor cells in patients with hepatocellular carcinoma using a novel cell separation strategy. Clin Cancer Res 2011;17:3783-93.
68. Olthoff KM, Forner A, Hübscher S, Fung J. What is the best staging system for hepatocellular carcinoma in the setting of liver transplantation? Liver Transpl 2011;17 Suppl 2:S26-33.
69. 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.
70. Fan ST, Yang ZF, Ho DWY, Ng MNP, Yu WC, Wong J. Prediction of posthepatectomy recurrence of hepatocellular carcinoma by circulating cancer stem cells: a prospective study. Ann Surg 2011;254:569-76.
71. Kim MY, Oskarsson T, Acharyya S, Nguyen DX, Zhang XHF, Norton L, Massagué J. Tumor self-seeding by circulating cancer cells. Cell 2009;139:1315-26.
72. Pantel K, Brakenhoff RH, Brandt B. Detection, clinical relevance and specific biological properties of disseminating tumour cells. Nat Rev Cancer 2008;8:329-40.
73. 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.
74. Tang JC, Feng YL, Guo T, Xie AY, Cai XJ. Circulating tumor DNA in hepatocellular carcinoma: trends and challenges. Cell Biosci 2016;6:32.
75. Heitzer E, Ulz P, Geigl JB. Circulating tumor DNA as a liquid biopsy for cancer. Clin Chem 2015;61:112-23.
76. Sausen M, Phallen J, Adleff V, Jones S, Leary RJ, Barrett MT, Anagnostou V, Parpart-Li S, Murphy D, Kay Li Q, Hruban CA, Scharpf R, White JR, O'Dwyer PJ, Allen PJ, Eshleman JR, Thompson CB, Klimstra DS, Linehan DC, Maitra A, Hruban RH, Diaz LA Jr, Von Hoff DD, Johansen JS, Drebin JA, Velculescu VE. Clinical implications of genomic alterations in the tumour and circulation of pancreatic cancer patients. Nat Commun 2015;6:7686.
77. Huang Z, Hua D, Hu Y, Cheng Z, Zhou X, Xie Q, Wang Q, Wang F, Du X, Zeng Y. Quantitation of plasma circulating DNA using quantitative PCR for the detection of hepatocellular carcinoma. Pathol Oncol Res 2012;18:271-6.
78. Chen H, Sun L, Zheng H, Zhang Q, Jin X. Total serum DNA and DNA integrity: diagnostic value in patients with hepatitis B virus-related hepatocellular carcinoma. Pathology 2012;44:318-24.
79. Mohamed NA, Swify EM, Amin NF, Soliman MM, Tag-Eldin LM, Elsherbiny NM. Is serum level of methylated RASSF1A valuable in diagnosing hepatocellular carcinoma in patients with chronic viral hepatitis C? Arab J Gastroenterol 2012;13:111-5.
80. Sun FK, Fan YC, Zhao J, Zhang F, Gao S, Zhao ZH, Sun Q, Wang K. Detection of TFPI2 methylation in the serum of hepatocellular carcinoma patients. Dig Dis Sci 2013;58:1010-5.
81. Earl J, Garcia-Nieto S, Martinez-Avila JC, Montans J, Sanjuanbenito A, Rodríguez-Garrote M, Lisa E, Mendía E, Lobo E, Malats N, Carrato A, Guillen-Ponce C. Circulating tumor cells (Ctc) and kras mutant circulating free Dna (cfdna) detection in peripheral blood as biomarkers in patients diagnosed with exocrine pancreatic cancer. BMC Cancer 2015;15:797.
82. Kinugasa H, Nouso K, Miyahara K, Morimoto Y, Dohi C, Tsutsumi K, Kato H, Matsubara T, Okada H, Yamamoto K. Detection of K-ras gene mutation by liquid biopsy in patients with pancreatic cancer. Cancer 2015;121:2271-80.
83. Villar S, Le Roux-Goglin E, Gouas DA, Plymoth A, Ferro G, Boniol M, Lereau M, Bah E, Hall AJ, Wild CP, Mendy M, Norder H, van der Sande M, Whittle H, Friesen MD, Groopman JD, Hainaut P. Seasonal variation in Tp53 R249S-mutated serum DNA with aflatoxin exposure and hepatitis B virus infection. Environ Health Perspect 2011;119:1635-40.
84. Kirk GD, Lesi OA, Mendy M, Szyma-ska K, Whittle H, Goedert JJ, Hainaut P, Montesano R. 249ser TP53 mutation in plasma DNA, hepatitis B viral infection, and risk of hepatocellular carcinoma. Oncogene 2005;24:5858-67.
85. Hosny G, Farahat N, Tayel H, Hainaut P. Ser-249 TP53 and CTNNB1 mutations in circulating free DNA of Egyptian patients with hepatocellular carcinoma versus chronic liver diseases. Cancer Lett 2008;264:201-8.
86. Hu J, Wang Z, Fan J, Dai Z, He Y, Qiu S, Huang X, Sun J, Xiao Y, Song K, Shi Y, Sun Q, Yang X, Shi G, Yu L, Yang G, Ding Z, Gao Q, Tang Z, Zhou J. Genetic variations in plasma circulating DNA of HBV-related hepatocellular carcinoma patients predict recurrence after liver transplantation. PLoS One 2011;6:e26003.
87. García-Fernández N, Macher HC, Rubio A, Jiménez-Arriscado P, Bellido-Díaz ML, Guerrero JM, Molinero P, Bernal-Bellido C, Suárez-Artacho G, Gómez-Bravo MA. Detection of p53 mutations in circulating DNA of transplanted hepatocellular carcinoma patients as a biomarker of tumor recurrence. Adv Exp Med Biol 2016;924:25-8.
88. Labgaa I, Villacorta-Martin C, D'Avola D, Craig AJ, von Felden J, Martins-Filho SN, Sia D, Stueck A, Ward SC, Fiel MI, Mahajan M, Tabrizian P, Thung SN, Ang C, Friedman SL, Llovet JM, Schwartz M, Villanueva A. A pilot study of ultra-deep targeted sequencing of plasma DNA identifies driver mutations in hepatocellular carcinoma. Oncogene 2018; doi: 10.1038/s41388-018-0206-3.
89. Chan KCA, Lai PBS, Mok TSK, Chan HLY, Ding C, Yeung SW, Lo YMD. Quantitative analysis of circulating methylated DNA as a biomarker for hepatocellular carcinoma. Clin Chem 2008;54:1528-36.
90. Huang ZH, Hu Y, Hua D, Wu YY, Song MX, Cheng ZH. Quantitative analysis of multiple methylated genes in plasma for the diagnosis and prognosis of hepatocellular carcinoma. Exp Mol Pathol 2011;91:702-7.
91. Huang A, Zhang X, Zhou SL, Cao Y, Huang XW, Fan J, Yang XR, Zhou J. Detecting circulating tumor DNA in hepatocellular carcinoma patients using droplet digital PCR is feasible and reflects intratumoral heterogeneity. J Cancer 2016;7:1907-14.
92. Xu RH, Wei W, Krawczyk M, Wang W, Luo H, Flagg K, Yi S, Shi W, Quan Q, Li K, Zheng L, Zhang H, Caughey BA, Zhao Q, Hou J, Zhang R, Xu Y, Cai H, Li G, Hou R, Zhong Z, Lin D, X2 Fu, Zhu J, Duan Y, Yu M, Ying B, Zhang W, Wang J, Zhang E, Zhang C, Li O, Guo R, Carter H, Zhu JK, Hao X, Zhang K. Circulating tumour DNA methylation markers for diagnosis and prognosis of hepatocellular carcinoma. Nat Mater 2017;16:1155-61.
93. Chen ZZ, Huang L, Wu YH, Zhai WJ, Zhu PP, Gao YF. LncSox4 promotes the self-renewal of liver tumour-initiating cells through Stat3-mediated Sox4 expression. Nat Commun 2016;7:12598.
94. Yuan SX, Wang J, Yang F, Tao fei Q, Zhang J, Wang li L, Yang Y, Liu H, Wang guang Z, Xu guo Q, Fan J, Liu L, Sun SH, Zhou WP. Long noncoding RNA DANCR increases stemness features of hepatocellular carcinoma by derepression of CTNNB1. Hepatology 2016;63:499-511.
95. Cao C, Sun J, Zhang D, Guo X, Xie L, Li X, Wu D, Liu L. The long intergenic noncoding RNA UFC1, a target of microRNA 34a, interacts with the mRNA stabilizing protein HuR to increase levels of β-catenin in HCC cells. Gastroenterology 2015;148:415-26.
96. Guo W, Liu S, Cheng Y, Lu L, Shi J, Xu G, Li N, Cheng K, Wu M, Cheng S, Liu S. ICAM-1-related noncoding RNA in cancer stem cells maintains ICAM-1 expression in hepatocellular carcinoma. Clin Cancer Res 2016;22:2041-50.
97. Wang X, Sun W, Shen W, Xia M, Chen C, Xiang D, Ning B, Cui X, Li H, Li X, Ding J, Wang H. Long non-coding RNA DILC regulates liver cancer stem cells via IL-6/STAT3 axis. J Hepatol 2016;64:1283-94.
98. Zhou CC, Yang F, Yuan x S, Ma JZ, Liu F, Yuan JH, Bi FR, Lin KY, Yin JH, Cao GW, Zhou WP, Wang F, Sun SH. Systemic genome screening identifies the outcome associated focal loss of long noncoding RNA PRAL in hepatocellular carcinoma. Hepatology 2016;63:850-63.
99. Romano G, Veneziano D, Acunzo M, Croce CM. Small non-coding RNA and cancer. Carcinogenesis 2017;38:485-91.
100. Bala S, Petrasek J, Mundkur S, Catalano D, Levin I, Ward J, Alao H, Kodys K, Szabo G. Circulating microRNAs in exosomes indicate hepatocyte injury and inflammation in alcoholic, drug-induced, and inflammatory liver diseases. Hepatology 2012;56:1946-57.
101. Jiang L, Li X, Cheng Q, Zhang BH. Plasma microRNA might as a potential biomarker for hepatocellular carcinoma and chronic liver disease screening. Tumour Biol 2015;36:7167-74.
102. Raposo G, Stoorvogel W. Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol 2013;200:373-83.
103. Théry C, Zitvogel L, Amigorena S. Exosomes: composition, biogenesis and function. Nat Rev Immunol 2002;2:569-79.
104. Yang X, Xie X, Xiao YF, Xie R, Hu CJ, Tang B, Li BS, Yang SM. The emergence of long non-coding RNAs in the tumorigenesis of hepatocellular carcinoma. Cancer Lett 2015;360:119-24.
105. Qiu MT, Hu JW, Yin R, Xu L. Long noncoding RNA: an emerging paradigm of cancer research. Tumor Biol 2013;34:613-20.
106. Lu J, Xie F, Geng L, Shen W, Sui C, Yang J. Investigation of serum lncRNA-uc003wbd and lncRNA-AF085935 expression profile in patients with hepatocellular carcinoma and HBV. Tumor Biol 2015;36:3231-6.
107. Tang J, Zhuo H, Zhang X, Jiang R, Ji J, Deng L, Qian X, Zhang F, Sun B. A novel biomarker Linc00974 interacting with KRT19 promotes proliferation and metastasis in hepatocellular carcinoma. Cell Death Dis 2014;5:e1549.
108. Jing W, Gao S, Zhu M, Luo P, Jing X, Chai H, Tu J. Potential diagnostic value of lncRNA SPRY4-IT1 in hepatocellular carcinoma. Oncol Rep 2016;36:1085-92.
109. Li SP, Xu HX, Yu Y, He JD, Wang Z, Xu YJ, Wang CY, Zhang HM, Zhang RX, Zhang JJ, Yao Z, Shen ZY. LncRNA HULC enhances epithelial-mesenchymal transition to promote tumorigenesis and metastasis of hepatocellular carcinoma via the miR-200a-3p/ZEB1 signaling pathway. Oncotarget 2016;7:42431-46.
110. Xie H, Ma H, Zhou D. Plasma HULC as a promising novel biomarker for the detection of hepatocellular carcinoma. Biomed Res Int 2013;2013:136106.
111. Lachenmayer A, Alsinet C, Savic R, Cabellos L, Toffanin S, Hoshida Y, Villanueva A, Minguez B, Newell P, Tsai HW, Barretina J, Thung S, Ward SC, Bruix J, Mazzaferro V, Schwartz M, Friedman SL, Llovet JM. Wnt-pathway activation in two molecular classes of hepatocellular carcinoma and experimental modulation by sorafenib. Clin Cancer Res 2012;18:4997-5007.
112. Ma X, Wang X, Yang C, Wang Z, Han B, Wu L, Zhuang L. DANCR acts as a diagnostic biomarker and promotes tumor growth and metastasis in hepatocellular carcinoma. Anticancer Res 2016;36:6389-98.
113. El-Tawdi AHF, Matboli M, El-Nakeep S, Azazy AEM, Abdel-Rahman O. Association of long noncoding RNA and c-JUN expression in hepatocellular carcinoma. Expert Rev Gastroenterol Hepatol 2016;10:869-77.
114. Kamel MM, Matboli M, Sallam M, Montasser IF, Saad AS, El-Tawdi AHF. Investigation of long noncoding RNAs expression profile as potential serum biomarkers in patients with hepatocellular carcinoma. Transl Res 2016;168:134-45.
115. Klingenberg M, Matsuda A, Diederichs S, Patel T. Non-coding RNA in hepatocellular carcinoma: Mechanisms, biomarkers and therapeutic targets. J Hepatol 2017;67:603-18.
116. Coulouarn C, Factor VM, Andersen JB, Durkin ME, Thorgeirsson SS. Loss of miR-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties. Oncogene 2009;28:3526-36.
117. Luo J, Chen M, Huang H, Yuan T, Zhang M, Zhang K, Deng S. Circulating microRNA-122a as a diagnostic marker for hepatocellular carcinoma. Onco Targets Ther 2013;6:577-83.
118. Xu J, Wu C, Che X, Wang L, Yu D, Zhang T, Huang L, Li H, Tan W, Wang C, Lin D. Circulating MicroRNAs, miR-21, miR-122, and miR-223, in patients with hepatocellular carcinoma or chronic hepatitis. Mol Carcinog 2011;50:136-42.
119. Kojima K, Takata A, Vadnais C, Otsuka M, Yoshikawa T, Akanuma M, Kondo Y, Kang YJ, Kishikawa T, Kato N, Xie Z, Zhang WJ, Yoshida H, Omata M, Nepveu A, Koike K. MicroRNA122 is a key regulator of α-fetoprotein expression and influences the aggressiveness of hepatocellular carcinoma. Nat Commun 2011;2:338.
120. Tan Y, Ge G, Pan T, Wen D, Chen L, Yu X, Zhou X, Gan J. A serum microrna panel as potential biomarkers for hepatocellular carcinoma related with hepatitis b virus. PLoS One 2014;9:e66577.
121. Ali HEA, Abdel Hameed R, Effat H, Ahmed EK, Atef AA, Sharawi SK, Ali M, Abd Elmageed ZY, Abdel Wahab AH. Circulating microRNAs panel as a diagnostic tool for discrimination of HCV-associated hepatocellular carcinoma. Clin Res Hepatol Gastroenterol 2017;41:e51-62.
122. Zekri ARN, Youssef ASED, El-Desouky ED, Ahmed OS, Lotfy MM, Nassar AAM, Bahnassey AA. Serum microRNA panels as potential biomarkers for early detection of hepatocellular carcinoma on top of HCV infection. Tumor Biol 2016;37:12273-86.
123. El-Tawdi AHF, Matboli M, Shehata HH, Tash F, El-Khazragy N, Azazy AESM, Abdel-Rahman O. Evaluation of circulatory RNA-based biomarker panel in hepatocellular carcinoma. Mol Diagnosis Ther 2016;20:265-77.
124. Okajima W, Komatsu S, Ichikawa D, Miyamae M, Kawaguchi T, Hirajima S, Ohashi T, Imamura T, Kiuchi J, Arita T, Konishi H, Shiozaki A, Moriumura R, Ikoma H, Okamoto K, Taniguchi H, Itoh Y, Otsuji E. Circulating microRNA profiles in plasma: identification of miR-224 as a novel diagnostic biomarker in hepatocellular carcinoma independent of hepatic function. Oncotarget 2016;7:53820-36.
125. Tomimaru Y, Eguchi H, Nagano H, Wada H, Kobayashi S, Marubashi S, Tanemura M, Tomokuni A, Takemasa I, Umeshita K, Kanto T, Doki Y, Mori M. Circulating microRNA-21 as a novel biomarker for hepatocellular carcinoma. J Hepatol 2012;56:167-75.
126. Huang JT, Liu SM, Ma H, Yang Y, Zhang X, Sun H, Zhang X, Xu J, Wang J. Systematic review and meta-analysis: circulating miRNAs for diagnosis of hepatocellular carcinoma. J Cell Physiol 2016;231:328-35.
127. Zhou L, Yang ZX, Song WJ, Li QJ, Yang F, Wang DS, Zhang N, Dou KF. MicroRNA-21 regulates the migration and invasion of a stem-like population in hepatocellular carcinoma. Int J Oncol 2013;43:661-9.
128. Wang J, Li J, Shen J, Wang C, Yang L, Zhang X. MicroRNA-182 downregulates metastasis suppressor 1 and contributes to metastasis of hepatocellular carcinoma. BMC Cancer 2012;12:227.
129. Becker A, Thakur BK, Weiss JM, Kim HS, Peinado H, Lyden D. Extracellular vesicles in cancer: cell-to-cell mediators of metastasis. Cancer Cell 2016;30:836-48.
130. Jia S, Zocco D, Samuels ML, Chou MF, Chammas R, Skog J, Zarovni N, Momen-Heravi F, Kuo WP. Emerging technologies in extracellular vesicle-based molecular diagnostics. Expert Rev Mol Diagn 2014;14:307-21.
131. Wendler F, Favicchio R, Simon T, Alifrangis C, Stebbing J, Giamas G. Extracellular vesicles swarm the cancer microenvironment: from tumor-stroma communication to drug intervention. Oncogene 2017;36:877-84.
132. Witwer KW, Buzás EI, Bemis LT, Bora A, Lässer C, Lötvall J, Nolte-’t Hoen EN, Piper MG, Sivaraman S, Skog J, Théry C, Wauben MH, Hochberg F. Standardization of sample collection, isolation and analysis methods in extracellular vesicle research. J Extracell Vesicles 2013;2:20360.
133. Conde-Vancells J, Rodriguez-Suarez E, Embade N, Gil D, Matthiesen R, Valle M, Elortza F, Lu SC, Mato JM, Falcon-Perez JM. Characterization and comprehensive proteome profiling of exosomes secreted by hepatocytes. J Proteome Res 2008;7:5157-66.
134. Willms A, Müller C, Julich H, Klein N, Schwab R, Güsgen C, Richardsen I, Schaaf S, Krawczyk M, Krawczyk M, Lammert F, Schuppan D, Lukacs-Kornek V, Kornek M. Tumour-associated circulating microparticles: a novel liquid biopsy tool for screening and therapy monitoring of colorectal carcinoma and other epithelial neoplasia. Oncotarget 2016;7:30867-75.
135. Abbate V, Marcantoni M, Giuliante F, Vecchio FM, Gatto I, Mele C, Saviano A, Arciuolo D, Gaetani E, Ferrari MC, Giarretta I, Ardito F, Riccardi L, Nicoletti A, Ponziani FR, Gasbarrini A, Pompili M, Pola R. HepPar1-positive circulating microparticles are increased in subjects with hepatocellular carcinoma and predict early recurrence after liver resection. Int J Mol Sci 2017;18:E1043.
136. Kornek M, Lynch M, Mehta SH, Lai M, Exley M, Afdhal NH, Schuppan D. Circulating microparticles as disease-specific biomarkers of severity of inflammation in patients with hepatitis C or nonalcoholic steatohepatitis. Gastroenterology 2012;143:448-58.
137. Julich-Haertel H, Urban SK, Krawczyk M, Willms A, Jankowski K, Patkowski W, Kruk B, Krasnodębski M, Ligocka J, Schwab R, Richardsen I, Schaaf S, Klein A, Gehlert S, Sänger H, Casper M, Banales JM, Schuppan D, Milkiewicz P, Lammert F, Krawczyk M, Lukacs-Kornek V, Kornek M. Cancer-associated circulating large extracellular vesicles in cholangiocarcinoma and hepatocellular carcinoma. J Hepatol 2017;67:282-92.
138. Berhane S, Toyoda H, Tada T, Kumada T, Kagebayashi C, Satomura S, Schweitzer N, Vogel A, Manns MP, Benckert J, Berg T, Ebker M, Best J, Dechêne A, Gerken G, Schlaak JF, Weinmann A, Wörns MA, Galle P, Yeo W, Mo F, Chan SL, Reeves H, Cox T, Johnson P. Role of the GALAD and BALAD-2 serologic models in diagnosis of hepatocellular carcinoma and prediction of survival in patients. Clin Gastroenterol Hepatol 2016;14:875-86.e6.