REFERENCES
1. Banini BA, Roberts LR. Hepatocellular carcinoma. Complications of Cirrhosis: Evaluation and management. Springer International Publishing; 2015. pp. 1-370.
2. Altekruse SF, McGlynn KA, Reichman ME. Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. J Clin Oncol 2009;27:1485-91.
3. Punnoose EA, Atwal SK, Spoerke JM, Savage H, Pandita A, et al. Molecular biomarker analyses using circulating tumor cells. PLoS One 2010;5:e12517.
4. 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.
5. Hirai H, Taketa K. Lectin affinity electrophoresis of alpha-fetoprotein. Increased specificity and sensitivity as a marker of hepatocellular carcinoma. J Chromatogr 1992;604:91-4.
6. Bruix J, Sherman M; American Association for the Study of Liver D. Management of hepatocellular carcinoma: an update. Hepatology 2011;53:1020-2.
7. Marrero JA, Feng Z, Wang Y, Nguyen MH, Befeler AS, et al. Alpha-fetoprotein, des-gamma carboxyprothrombin, and lectin-bound alpha-fetoprotein in early hepatocellular carcinoma. Gastroenterology 2009;137:110-8.
8. 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.
9. Farinati F, Marino D, De Giorgio M, Baldan A, Cantarini M, et al. Diagnostic and prognostic role of alpha-fetoprotein in hepatocellular carcinoma: both or neither? Am J Gastroenterol 2006;101:524-32.
10. Mandel P, Metais P. Les acides nucléiques du plasma sanguin chez l’homme. C R Seances Soc Biol Fil 1948;142:241-3.
11. 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.
12. Vasioukhin V, Anker P, Maurice P, Lyautey J, Lederrey C, et al. Point mutations of the N-ras gene in the blood plasma DNA of patients with myelodysplastic syndrome or acute myelogenous leukaemia. Br J Haematol 1994;86:774-9.
13. Cachia PG, Taylor C, Thompson PW, Tennant GB, Masters G, et al. Non-dysplastic myelodysplasia? Leukemia 1994;8:677-81.
14. Sorenson GD, Pribish DM, Valone FH, Memoli VA, Bzik DJ, et al. Soluble normal and mutated DNA sequences from single-copy genes in human blood. Cancer Epidemiol Biomarkers Prev 1994;3:67-71.
15. Matsumura M, Shiratori Y, Niwa Y, Tanaka T, Ogura K, et al. Presence of alpha-fetoprotein mRNA in blood correlates with outcome in patients with hepatocellular carcinoma. J Hepatol 1999;31:332-9.
16. Cillo U, Navaglia F, Vitale A, Molari A, Basso D, et al. Clinical significance of alpha-fetoprotein mRNA in blood of patients with hepatocellular carcinoma. Clin Chim Acta 2004;347:129-38.
17. Jeng KS, Sheen IS, Tsai YC. Does the presence of circulating hepatocellular carcinoma cells indicate a risk of recurrence after resection? Am J Gastroenterol 2004;99:1503-9.
18. 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.
19. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A 2008;105:10513-8.
20. Zheng Q, Zhao J, Yu H, Zong H, He X, et al. Tumor-specific transcripts are frequently expressed in hepatocellular carcinoma with clinical implication and potential function. Hepatology 2019; doi: 10.1002/hep.30805.
21. Koduru SV, Leberfinger AN, Kawasawa YI, Mahajan M, Gusani NJ, et al. Non-coding RNAs in various stages of liver disease leading to hepatocellular carcinoma: differential expression of miRNAs, piRNAs, lncRNAs, circRNAs, and sno/mt-RNAs. Sci Rep 2018;8:7967.
22. Tian XP, Wang CY, Jin XH, Li M, Wang FW, et al. Acidic microenvironment up-regulates exosomal miR-21 and miR-10b in early-stage hepatocellular carcinoma to promote cancer cell proliferation and metastasis. Theranostics 2019;9:1965-79.
23. Koberle V, Kronenberger B, Pleli T, Trojan J, Imelmann E, et al. Serum microRNA-1 and microRNA-122 are prognostic markers in patients with hepatocellular carcinoma. Eur J Cancer 2013;49:3442-9.
24. Qu KZ, Zhang K, Li H, Afdhal NH, Albitar M. Circulating microRNAs as biomarkers for hepatocellular carcinoma. J Clin Gastroenterol 2011;45:355-60.
25. Ge W, Yu DC, Li QG, Chen X, Zhang CY, et al. Expression of serum miR-16, let-7f, and miR-21 in patients with hepatocellular carcinoma and their clinical significances. Clin Lab 2014;60:427-34.
26. El-Abd NE, Fawzy NA, El-Sheikh SM, Soliman ME. Circulating miRNA-122, miRNA-199a, and miRNA-16 as biomarkers for early detection of hepatocellular carcinoma in egyptian patients with chronic hepatitis C virus infection. Mol Diagn Ther 2015;19:213-20.
27. Qi P, Cheng SQ, Wang H, Li N, Chen YF, et al. Serum microRNAs as biomarkers for hepatocellular carcinoma in Chinese patients with chronic hepatitis B virus infection. PLoS One 2011;6:e28486.
28. Liu M, Liu J, Wang L, Wu H, Zhou C, et al. Association of serum microRNA expression in hepatocellular carcinomas treated with transarterial chemoembolization and patient survival. PLoS One 2014;9:e109347.
29. Zekri AN, Youssef AS, El-Desouky ED, Ahmed OS, Lotfy MM, et al. Serum microRNA panels as potential biomarkers for early detection of hepatocellular carcinoma on top of HCV infection. Tumour Biol 2016;37:12273-86.
30. Mirzaei HR, Sahebkar A, Mohammadi M, Yari R, Salehi H, et al. Circulating microRNAs in hepatocellular carcinoma: potential diagnostic and prognostic biomarkers. Curr Pharm Des 2016;22:5257-69.
31. Forshew T, Murtaza M, Parkinson C, Gale D, Tsui DW, et al. Noninvasive identification and monitoring of cancer mutations by targeted deep sequencing of plasma DNA. Sci Transl Med 2012;4:136ra68.
32. Newman AM, Bratman SV, To J, Wynne JF, Eclov NC, et al. An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage. Nat Med 2014;20:548-54.
33. Chen H, Sun LY, Zheng HQ, Zhang QF, Jin XM. Total serum DNA and DNA integrity: diagnostic value in patients with hepatitis B virus-related hepatocellular carcinoma. Pathology 2012;44:318-24.
34. Huang Z, Hua D, Hu Y, Cheng Z, Zhou X, et al. Quantitation of plasma circulating DNA using quantitative PCR for the detection of hepatocellular carcinoma. Pathol Oncol Res 2012;18:271-6.
35. Chan KC, Jiang P, Zheng YW, Liao GJ, Sun H, et al. Cancer genome scanning in plasma: detection of tumor-associated copy number aberrations, single-nucleotide variants, and tumoral heterogeneity by massively parallel sequencing. Clin Chem 2013;59:211-24.
36. Jiang P, Chan CW, Chan KC, Cheng SH, Wong J, et al. Lengthening and shortening of plasma DNA in hepatocellular carcinoma patients. Proc Natl Acad Sci U S A 2015;112:E1317-25.
37. Wong IH, Lo YM, Yeo W, Lau WY, Johnson PJ. Frequent p15 promoter methylation in tumor and peripheral blood from hepatocellular carcinoma patients. Clin Cancer Res 2000;6:3516-21.
38. Ren N, Qin LX, Tu H, Liu YK, Zhang BH, et al. The prognostic value of circulating plasma DNA level and its allelic imbalance on chromosome 8p in patients with hepatocellular carcinoma. J Cancer Res Clin Oncol 2006;132:399-407.
39. Iizuka N, Sakaida I, Moribe T, Fujita N, Miura T, et al. Elevated levels of circulating cell-free DNA in the blood of patients with hepatitis C virus-associated hepatocellular carcinoma. Anticancer Res 2006;26:4713-9.
40. Piciocchi M, Cardin R, Vitale A, Vanin V, Giacomin A, et al. Circulating free DNA in the progression of liver damage to hepatocellular carcinoma. Hepatol Int 2013;7:1050-7.
41. Yan L, Chen Y, Zhou J, Zhao H, Zhang H, et al. Diagnostic value of circulating cell-free DNA levels for hepatocellular carcinoma. Int J Infect Dis 2018;67:92-7.
42. Szymanska K, Chen JG, Cui Y, Gong YY, Turner PC, et al. TP53 R249S mutations, exposure to aflatoxin, and occurrence of hepatocellular carcinoma in a cohort of chronic hepatitis B virus carriers from Qidong, China. Cancer Epidemiol Biomarkers Prev 2009;18:1638-43.
43. Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y, et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med 2014;6:224ra24.
44. Yu L, Liu X, Han C, Lu S, Zhu G, et al. XRCC1 rs25487 genetic variant and TP53 mutation at codon 249 predict clinical outcomes of hepatitis B virus-related hepatocellular carcinoma after hepatectomy: a cohort study for 10 years’ follow up. Hepatol Res 2016;46:765-74.
45. Cai ZX, Chen G, Zeng YY, Dong XQ, Lin MJ, et al. Circulating tumor DNA profiling reveals clonal evolution and real-time disease progression in advanced hepatocellular carcinoma. Int J Cancer 2017;141:977-85.
46. Huang A, Zhang X, Zhou SL, Cao Y, Huang XW, et al. Detecting circulating tumor DNA in hepatocellular carcinoma patients using droplet digital PCR is feasible and reflects intratumoral heterogeneity. J Cancer 2016;7:1907-14.
47. Nault JC, Zucman-Rossi J. Genetics of hepatocellular carcinoma: the next generation. J Hepatol 2014;60:224-6.
48. Kan Z, Zheng H, Liu X, Li S, Barber TD, et al. Whole-genome sequencing identifies recurrent mutations in hepatocellular carcinoma. Genome Res 2013;23:1422-33.
49. Fujimoto A, Totoki Y, Abe T, Boroevich KA, Hosoda F, et al. Whole-genome sequencing of liver cancers identifies etiological influences on mutation patterns and recurrent mutations in chromatin regulators. Nat Genet 2012;44:760-4.
50. Nault JC, Mallet M, Pilati C, Calderaro J, Bioulac-Sage P, et al. High frequency of telomerase reverse-transcriptase promoter somatic mutations in hepatocellular carcinoma and preneoplastic lesions. Nat Commun 2013;4:2218.
51. Nault JC, Calderaro J, Di Tommaso L, Balabaud C, Zafrani ES, et al. Telomerase reverse transcriptase promoter mutation is an early somatic genetic alteration in the transformation of premalignant nodules in hepatocellular carcinoma on cirrhosis. Hepatology 2014;60:1983-92.
52. Pinyol R, Tovar V, Llovet JM. TERT promoter mutations: gatekeeper and driver of hepatocellular carcinoma. J Hepatol 2014;61:685-7.
53. 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.
54. 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.
55. Kuang SY, Lekawanvijit S, Maneekarn N, Thongsawat S, Brodovicz K, et al. Hepatitis B 1762T/1764A mutations, hepatitis C infection, and codon 249 p53 mutations in hepatocellular carcinomas from Thailand. Cancer Epidemiol Biomarkers Prev 2005;14:380-4.
56. Szymanska K, Lesi OA, Kirk GD, Sam O, Taniere P, et al. Ser-249TP53 mutation in tumour and plasma DNA of hepatocellular carcinoma patients from a high incidence area in the Gambia, West Africa. Int J Cancer 2004;110:374-9.
57. Lleonart ME, Kirk GD, Villar S, Lesi OA, Dasgupta A, et al. Quantitative analysis of plasma TP53 249Ser-mutated DNA by electrospray ionization mass spectrometry. Cancer Epidemiol Biomarkers Prev 2005;14:2956-62.
58. Ikeda S, Tsigelny IF, Skjevik AA, Kono Y, Mendler M, et al. Next-generation sequencing of circulating tumor DNA reveals frequent alterations in advanced hepatocellular carcinoma. Oncologist 2018;23:586-93.
59. Cohen JD, Li L, Wang Y, Thoburn C, Afsari B, et al. Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science 2018;359:926-30.
60. Ono A, Fujimoto A, Yamamoto Y, Akamatsu S, Hiraga N, et al. Circulating tumor DNA analysis for liver cancers and its usefulness as a liquid biopsy. Cell Mol Gastroenterol Hepatol 2015;1:516-34.
61. Huang A, Zhang X, Zhou SL, Cao Y, Huang XW, et al. Plasma Circulating cell-free DNA integrity as a promising biomarker for diagnosis and surveillance in patients with hepatocellular carcinoma. J Cancer 2016;7:1798-803.
62. Pang JZ, Qin LX, Wang QQ, Ren N, Sun BS, et al. Loss of heterozygosity of plasma circulating DNA from hepatocellular carcinoma patients and its clinical significance. Zhonghua Gan Zang Bing Za Zhi 2007;15:906-9.
63. Pang JZ, Qin LX, Ren N, Ye QH, Ying WD, et al. Microsatellite alterations of circulating DNA in the plasma of patients with hepatocellular carcinoma. Zhonghua Yi Xue Za Zhi 2006;86:1662-5.
64. Zhang YJ, Wu HC, Shen J, Ahsan H, Tsai WY, et al. Predicting hepatocellular carcinoma by detection of aberrant promoter methylation in serum DNA. Clin Cancer Res 2007;13:2378-84.
65. Iyer P, Zekri AR, Hung CW, Schiefelbein E, Ismail K, et al. Concordance of DNA methylation pattern in plasma and tumor DNA of Egyptian hepatocellular carcinoma patients. Exp Mol Pathol 2010;88:107-11.
66. Iizuka N, Oka M, Sakaida I, Moribe T, Miura T, et al. Efficient detection of hepatocellular carcinoma by a hybrid blood test of epigenetic and classical protein markers. Clin Chim Acta 2011;412:152-8.
67. Huang ZH, Hu Y, Hua D, Wu YY, Song MX, et al. Quantitative analysis of multiple methylated genes in plasma for the diagnosis and prognosis of hepatocellular carcinoma. Exp Mol Pathol 2011;91:702-7.
68. Sun FK, Fan YC, Zhao J, Zhang F, Gao S, et al. Detection of TFPI2 methylation in the serum of hepatocellular carcinoma patients. Dig Dis Sci 2013;58:1010-5.
69. Chang H, Yi B, Li L, Zhang HY, Sun F, et al. Methylation of tumor associated genes in tissue and plasma samples from liver disease patients. Exp Mol Pathol 2008;85:96-100.
70. Yeo W, Wong N, Wong WL, Lai PB, Zhong S, et al. High frequency of promoter hypermethylation of RASSF1A in tumor and plasma of patients with hepatocellular carcinoma. Liver Int 2005;25:266-72.
71. Borowa-Mazgaj B, de Conti A, Tryndyak V, Steward CR, Jimenez L, et al. Gene expression and DNA methylation alterations in the glycine N-methyltransferase gene in diet-induced nonalcoholic fatty liver disease-associated carcinogenesis. Toxicol Sci 2019; doi: 10.1093/toxsci/kfz110.
72. Tangkijvanich P, Hourpai N, Rattanatanyong P, Wisedopas N, Mahachai V, et al. Serum LINE-1 hypomethylation as a potential prognostic marker for hepatocellular carcinoma. Clin Chim Acta 2007;379:127-33.
73. Mohamed NA, Swify EM, Amin NF, Soliman MM, Tag-Eldin LM, et al. 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.
