Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2018

Open Access 01-12-2018 | Review

Clinical applications of liquid biopsy as prognostic and predictive biomarkers in hepatocellular carcinoma: circulating tumor cells and circulating tumor DNA

Authors: Jie Li, Xu Han, Xiaona Yu, Zongzhen Xu, Guangsheng Yang, Bingqi Liu, Peng Xiu

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2018

Login to get access

Abstract

Hepatocellular carcinoma (HCC) is a highly malignant disease with a poor prognosis and high mortality due to a low early diagnosis rate, resistance to systemic treatments and progression to late-stage liver disease. Owing to limitations in the detection of HCC and the lack of awareness of healthcare systems, fewer than 40% of HCC patients are eligible for surgery due to advanced stages of the disease at the time of diagnosis and the occurrence of multiple lesions in the cirrhotic or fibrotic liver. At present, the updated American Association for the Study of Liver Disease (AASLD) guidelines no longer recommend alpha-fetoprotein (AFP) testing as a part of diagnostic evaluation. Thus, it is imperative to establish a novel diagnostic strategy with high sensitivity and reliability to monitor risk factors to detect HCC at an early stage. In recent years, “liquid biopsy,” (including circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA)), has emerged as a technique for the characterization of circulating cells, providing a strong basis for the individualized treatment of patients. As a noninvasive detection method, liquid biopsy is expected to play an important role in the early diagnosis, dynamic monitoring of cancer patients and drug screening. In this review, we will focus on the clinical applications, recent studies and future prospects of liquid biopsy, particularly focusing on HCC.
Literature
1.
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108.PubMedCrossRef
2.
3.
Fattovich G, Stroffolini T, Zagni I, Donato F. Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology. 2004;127(5 Suppl 1):S35–50.PubMedCrossRef
4.
5.
Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66(2):115–32.PubMedCrossRef
6.
7.
El-Serag HB, Marrero JA, Rudolph L, Reddy KR. Diagnosis and treatment of hepatocellular carcinoma. Gastroenterology. 2008;134(6):1752–63.PubMedCrossRef
8.
Zamcheck N, Pusztaszeri G. CEA, AFP and other potential tumor markers. CA Cancer J Clin. 1975;25(4):204–14.PubMedCrossRef
9.
10.
11.
Gerlinger M, Rowan AJ, Horswell S, Math M, Larkin J, Endesfelder D, Gronroos E, Martinez P, Matthews N, Stewart A, et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med. 2012;366(10):883–92.PubMedPubMedCentralCrossRef
12.
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.
13.
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.PubMedPubMedCentral
14.
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;2010:617421.PubMedCrossRef
15.
Low WS, Wan Abas WA. Benchtop technologies for circulating tumor cells separation based on biophysical properties. Biomed Res Int. 2015;2015:239362.PubMedPubMedCentral
16.
Hou HW, Warkiani ME, Khoo BL, Li ZR, Soo RA, Tan DS, Lim WT, Han J, Bhagat AA, Lim CT. Isolation and retrieval of circulating tumor cells using centrifugal forces. Sci Rep. 2013;3:1259.PubMedPubMedCentralCrossRef
17.
Alix-Panabieres C, Pantel K. Challenges in circulating tumour cell research. Nat Rev Cancer. 2014;14(9):623–31.PubMedCrossRef
18.
Pantel K, Alix-Panabieres C. Real-time liquid biopsy in cancer patients: fact or fiction? Cancer Res. 2013;73(21):6384–8.PubMedCrossRef
19.
Pantel K, Alix-Panabieres C. The clinical significance of circulating tumor cells. Nat Clin Pract Oncol. 2007;4(2):62–3.PubMedCrossRef
20.
Riethdorf S, Fritsche H, Muller V, Rau T, Schindlbeck C, Rack B, Janni W, Coith C, Beck K, Janicke F, et al. Detection of circulating tumor cells in peripheral blood of patients with metastatic breast cancer: a validation study of the CellSearch system. Clin Cancer Res. 2007;13(3):920–8.PubMedCrossRef
21.
Lin PP. Integrated EpCAM-independent subtraction enrichment and iFISH strategies to detect and classify disseminated and circulating tumors cells. Clin Transl Med. 2015;4(1):38.PubMedPubMedCentralCrossRef
22.
Matsumura M, Niwa Y, Kato N, Komatsu Y, Shiina S, Kawabe T, Kawase T, Toyoshima H, Ihori M, Shiratori Y, et al. Detection of alpha-fetoprotein mRNA, an indicator of hematogenous spreading hepatocellular carcinoma, in the circulation: a possible predictor of metastatic hepatocellular carcinoma. Hepatology. 1994;20(6):1418–25.PubMedCrossRef
23.
Matsumura M, Shiratori Y, Niwa Y, Tanaka T, Ogura K, Okudaira T, Imamura M, Okano K, Shiina S, Omata M. Presence of alpha-fetoprotein mRNA in blood correlates with outcome in patients with hepatocellular carcinoma. J Hepatol. 1999;31(2):332–9.PubMedCrossRef
24.
Lemoine A, Le Bricon T, Salvucci M, Azoulay D, Pham P, Raccuia J, Bismuth H, Debuire B. Prospective evaluation of circulating hepatocytes by alpha-fetoprotein mRNA in humans during liver surgery. Ann Surg. 1997;226(1):43–50.PubMedPubMedCentralCrossRef
25.
Wong IH, Yeo W, Leung T, Lau WY, Johnson PJ. Circulating tumor cell mRNAs in peripheral blood from hepatocellular carcinoma patients under radiotherapy, surgical resection or chemotherapy: a quantitative evaluation. Cancer Lett. 2001;167(2):183–91.PubMedCrossRef
26.
Witzigmann H, Geissler F, Benedix F, Thiery J, Uhlmann D, Tannapfel A, Wittekind C, Hauss J. Prospective evaluation of circulating hepatocytes by alpha-fetoprotein messenger RNA in patients with hepatocellular carcinoma. Surgery. 2002;131(1):34–43.PubMedCrossRef
27.
Cillo U, Navaglia F, Vitale A, Molari A, Basso D, Bassanello M, Brolese A, Zanus G, Montin U, D'Amico F, et al. Clinical significance of alpha-fetoprotein mRNA in blood of patients with hepatocellular carcinoma. Clin Chim Acta. 2004;347(1–2):129–38.PubMedCrossRef
28.
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(8):1503–9.PubMedCrossRef
29.
Kong SY, Park JW, Kim JO, Lee NO, Lee JA, Park KW, Hong EK, Kim CM. Alpha-fetoprotein and human telomerase reverse transcriptase mRNA levels in peripheral blood of patients with hepatocellular carcinoma. J Cancer Res Clin Oncol. 2009;135(8):1091–8.PubMedCrossRef
30.
Jin J, Niu X, Zou L, Li L, Li S, Han J, Zhang P, Song J, Xiao F. AFP mRNA level in enriched circulating tumor cells from hepatocellular carcinoma patient blood samples is a pivotal predictive marker for metastasis. Cancer Lett. 2016;378(1):33–7.PubMedCrossRef
31.
Mou DC, Cai SL, Peng JR, Wang Y, Chen HS, Pang XW, Leng XS, Chen WF. Evaluation of MAGE-1 and MAGE-3 as tumour-specific markers to detect blood dissemination of hepatocellular carcinoma cells. Br J Cancer. 2002;86(1):110–6.PubMedPubMedCentralCrossRef
32.
Yao M, Yao DF, Bian YZ, Wu W, Yan XD, Yu DD, Qiu LW, Yang JL, Zhang HJ, Sai WL, et al. Values of circulating GPC-3 mRNA and alpha-fetoprotein in detecting patients with hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int. 2013;12(2):171–9.PubMedCrossRef
33.
Bahnassy AA, Zekri AR, El-Bastawisy A, Fawzy A, Shetta M, Hussein N, Omran D, Ahmed AA, El-Labbody SS. Circulating tumor and cancer stem cells in hepatitis C virus-associated liver disease. World J Gastroenterol. 2014;20(48):18240–8.PubMedPubMedCentralCrossRef
34.
Choi GH, Kim GI, Yoo JE, Na DC, Han DH, Roh YH, Park YN, Choi JS. Increased expression of circulating Cancer stem cell markers during the perioperative period predicts early recurrence after curative resection of hepatocellular carcinoma. Ann Surg Oncol. 2015;22(Suppl 3):S1444–52.PubMedCrossRef
35.
Guo L, Xu D, Lu Y, Peng J, Jiang L. Detection of circulating tumor cells by reverse transcriptionquantitative polymerase chain reaction and magnetic activated cell sorting in the peripheral blood of patients with hepatocellular carcinoma. Mol Med Rep. 2017;16(5):5894–900.PubMedPubMedCentralCrossRef
36.
Vona G, Sabile A, Louha M, Sitruk V, Romana S, Schutze K, Capron F, Franco D, Pazzagli M, Vekemans M, et al. Isolation by size of epithelial tumor cells : a new method for the immunomorphological and molecular characterization of circulatingtumor cells. Am J Pathol. 2000;156(1):57–63.PubMedPubMedCentralCrossRef
37.
Morris KL, Tugwood JD, Khoja L, Lancashire M, Sloane R, Burt D, Shenjere P, Zhou C, Hodgson C, Ohtomo T, et al. Circulating biomarkers in hepatocellular carcinoma. Cancer Chemother Pharmacol. 2014;74(2):323–32.PubMedCrossRef
38.
Wang Z, Luo L, Cheng Y, He G, Peng B, Gao Y, Jiang ZS, Pan M. Correlation between postoperative early recurrence of hepatocellular carcinoma and Mesenchymal circulating tumor cells in peripheral blood. J Gastrointest Surg. 2018;22(4):633–39.PubMedCrossRef
39.
Chen J, Cao SW, Cai Z, Zheng L, Wang Q. Epithelial-mesenchymal transition phenotypes of circulating tumor cells correlate with the clinical stages and cancer metastasis in hepatocellular carcinoma patients. Cancer Biomark. 2017;20(4):487–98.PubMedCrossRef
40.
Sun YF, Xu Y, Yang XR, Guo W, Zhang X, Qiu SJ, Shi RY, Hu B, Zhou J, Fan J. Circulating stem cell-like epithelial cell adhesion molecule-positive tumor cells indicate poor prognosis of hepatocellular carcinoma after curative resection. Hepatology. 2013;57(4):1458–68.PubMedCrossRef
41.
Schulze K, Gasch C, Staufer K, Nashan B, Lohse AW, Pantel K, Riethdorf S, Wege H. Presence of EpCAM-positive circulating tumor cells as biomarker for systemic disease strongly correlates to survival in patients with hepatocellular carcinoma. Int J Cancer. 2013;133(9):2165–71.PubMedCrossRef
42.
Kelley RK, Magbanua MJ, Butler TM, Collisson EA, Hwang J, Sidiropoulos N, Evason K, McWhirter RM, Hameed B, Wayne EM, et al. Circulating tumor cells in hepatocellular carcinoma: a pilot study of detection, enumeration, and next-generation sequencing in cases and controls. BMC Cancer. 2015;15:206.PubMedPubMedCentralCrossRef
43.
Went PT, Lugli A, Meier S, Bundi M, Mirlacher M, Sauter G, Dirnhofer S. Frequent EpCam protein expression in human carcinomas. Hum Pathol. 2004;35(1):122–8.PubMedCrossRef
44.
Xu W, Cao L, Chen L, Li J, Zhang XF, Qian HH, Kang XY, Zhang Y, Liao J, Shi LH, et al. Isolation of circulating tumor cells in patients with hepatocellular carcinoma using a novel cell separation strategy. Clin Cancer Res. 2011;17(11):3783–93.PubMedCrossRef
45.
Li J, Chen L, Zhang X, Zhang Y, Liu H, Sun B, Zhao L, Ge N, Qian H, Yang Y, et al. Detection of circulating tumor cells in hepatocellular carcinoma using antibodies against asialoglycoprotein receptor, carbamoyl phosphate synthetase 1 and pan-cytokeratin. PLoS One. 2014;9(4):e96185.PubMedPubMedCentralCrossRef
46.
Liu HY, Qian HH, Zhang XF, Li J, Yang X, Sun B, Ma JY, Chen L, Yin ZF. Improved method increases sensitivity for circulating hepatocellular carcinoma cells. World J Gastroenterol. 2015;21(10):2918–25.PubMedPubMedCentralCrossRef
47.
Liu Z, Guo W, Zhang D, Pang Y, Shi J, Wan S, Cheng K, Wang J, Cheng S. Circulating tumor cell detection in hepatocellular carcinoma based on karyoplasmic ratios using imaging flow cytometry. Sci Rep. 2016;6:39808.PubMedPubMedCentralCrossRef
48.
Li J, Shi L, Zhang X, Sun B, Yang Y, Ge N, Liu H, Yang X, Chen L, Qian H, et al. pERK/pAkt phenotyping in circulating tumor cells as a biomarker for sorafenib efficacy in patients with advanced hepatocellular carcinoma. Oncotarget. 2016;7(3):2646–59.PubMed
49.
Li YM, Xu SC, Li J, Han KQ, Pi HF, Zheng L, Zuo GH, Huang XB, Li HY, Zhao HZ, et al. Epithelial-mesenchymal transition markers expressed in circulating tumor cells in hepatocellular carcinoma patients with different stages of disease. Cell Death Dis. 2013;4:e831.PubMedPubMedCentralCrossRef
50.
Shi J, Li Y, Liang S, Zeng J, Liu G, Mu F, Li H, Chen J, Lin M, Sheng S, et al. Circulating tumour cells as biomarkers for evaluating cryosurgery on unresectable hepatocellular carcinoma. Oncol Rep. 2016;36(4):1845–51.PubMedCrossRef
51.
Ogle LF, Orr JG, Willoughby CE, Hutton C, McPherson S, Plummer R, Boddy AV, Curtin NJ, Jamieson D, Reeves HL. Imagestream detection and characterisation of circulating tumour cells - a liquid biopsy for hepatocellular carcinoma? J Hepatol. 2016;65(2):305–13.PubMedCrossRef
52.
Julich-Haertel H, Urban SK, Krawczyk M, Willms A, Jankowski K, Patkowski W, Kruk B, Krasnodebski M, Ligocka J, Schwab R, et al. Cancer-associated circulating large extracellular vesicles in cholangiocarcinoma and hepatocellular carcinoma. J Hepatol. 2017;67(2):282–92.PubMedCrossRef
53.
Liu S, Li N, Yu X, Xiao X, Cheng K, Hu J, Wang J, Zhang D, Cheng S, Liu S. Expression of intercellular adhesion molecule 1 by hepatocellular carcinoma stem cells and circulating tumor cells. Gastroenterology. 2013;144(5):1031–1041 e1010.PubMedCrossRef
54.
Kalinich M, Bhan I, Kwan TT, Miyamoto DT, Javaid S, LiCausi JA, Milner JD, Hong X, Goyal L, Sil S, et al. An RNA-based signature enables high specificity detection of circulating tumor cells in hepatocellular carcinoma. Proc Natl Acad Sci U S A. 2017;114(5):1123–8.PubMedPubMedCentralCrossRef
55.
Zhang Y, Zhang X, Zhang J, Sun B, Zheng L, Li J, Liu S, Sui G, Yin Z. Microfluidic chip for isolation of viable circulating tumor cells of hepatocellular carcinoma for their culture and drug sensitivity assay. Cancer Biol Ther. 2016;17(11):1177–87.PubMedPubMedCentralCrossRef
56.
Wang S, Zhang C, Wang G, Cheng B, Wang Y, Chen F, Chen Y, Feng M, Xiong B. Aptamer-mediated transparent-biocompatible nanostructured surfaces for Hepotocellular circulating tumor cells enrichment. Theranostics. 2016;6(11):1877–86.PubMedPubMedCentralCrossRef
57.
Sun C, Liao W, Deng Z, Li E, Feng Q, Lei J, Yuan R, Zou S, Mao Y, Shao J, et al. The diagnostic value of assays for circulating tumor cells in hepatocellular carcinoma: a meta-analysis. Medicine. 2017;96(29):e7513.PubMedPubMedCentralCrossRef
58.
Raponi M, Dossey L, Jatkoe T, Wu X, Chen G, Fan H, Beer DG. MicroRNA classifiers for predicting prognosis of squamous cell lung cancer. Cancer Res. 2009;69(14):5776–83.PubMedCrossRef
59.
Leon SA, Ehrlich GE, Shapiro B, Labbate VA. Free DNA in the serum of rheumatoid arthritis patients. J Rheumatol. 1977;4(2):139–43.PubMed
60.
Fleischhacker M, Schmidt B. Circulating nucleic acids (CNAs) and cancer--a survey. Biochim Biophys Acta. 2007;1775(1):181–232.PubMed
61.
Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y, Agrawal N, Bartlett BR, Wang H, Luber B, Alani RM, et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 2014;6(224):224ra224.CrossRef
62.
Diehl F, Schmidt K, Choti MA, Romans K, Goodman S, Li M, Thornton K, Agrawal N, Sokoll L, Szabo SA, et al. Circulating mutant DNA to assess tumor dynamics. Nat Med. 2008;14(9):985–90.PubMedCrossRef
63.
Tamkovich SN, Cherepanova AV, Kolesnikova EV, Rykova EY, Pyshnyi DV, Vlassov VV, Laktionov PP. Circulating DNA and DNase activity in human blood. Ann N Y Acad Sci. 2006;1075:191–6.PubMedCrossRef
64.
Lee TH, Montalvo L, Chrebtow V, Busch MP. Quantitation of genomic DNA in plasma and serum samples: higher concentrations of genomic DNA found in serum than in plasma. Transfusion. 2001;41(2):276–82.PubMedCrossRef
65.
Jung M, Klotzek S, Lewandowski M, Fleischhacker M, Jung K. Changes in concentration of DNA in serum and plasma during storage of blood samples. Clin Chem. 2003;49(6 Pt 1):1028–9.PubMedCrossRef
66.
Volik S, Alcaide M, Morin RD, Collins C. Cell-free DNA (cfDNA): clinical significance and utility in Cancer shaped by emerging technologies. Mol Cancer Res. 2016;14(10):898–908.PubMedCrossRef
67.
Vallee A, Marcq M, Bizieux A, Kouri CE, Lacroix H, Bennouna J, Douillard JY, Denis MG. Plasma is a better source of tumor-derived circulating cell-free DNA than serum for the detection of EGFR alterations in lung tumor patients. Lung Cancer. 2013;82(2):373–4.PubMedCrossRef
68.
van Dessel LF, Beije N, Helmijr JC, Vitale SR, Kraan J, Look MP, de Wit R, Sleijfer S, Jansen MP, Martens JW, et al. Application of circulating tumor DNA in prospective clinical oncology trials - standardization of preanalytical conditions. Mol Oncol. 2017;11(3):295–304.PubMedPubMedCentralCrossRef
69.
70.
Forshew T, Murtaza M, Parkinson C, Gale D, Tsui DW, Kaper F, Dawson SJ, Piskorz AM, Jimenez-Linan M, Bentley D, et al. Noninvasive identification and monitoring of cancer mutations by targeted deep sequencing of plasma DNA. Sci Transl Med. 2012;4(136):136ra168.CrossRef
71.
Newman AM, Bratman SV, To J, Wynne JF, Eclov NC, Modlin LA, Liu CL, Neal JW, Wakelee HA, Merritt RE, et al. An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage. Nat Med. 2014;20(5):548–54.PubMedPubMedCentralCrossRef
72.
Ren N, Qin LX, Tu H, Liu YK, Zhang BH, Tang ZY. 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(6):399–407.PubMedCrossRef
73.
Iizuka N, Sakaida I, Moribe T, Fujita N, Miura T, Stark M, Tamatsukuri S, Ishitsuka H, Uchida K, Terai S, 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(6C):4713–9.PubMed
74.
Yang YJ, Chen H, Huang P, Li CH, Dong ZH, Hou YL. Quantification of plasma hTERT DNA in hepatocellular carcinoma patients by quantitative fluorescent polymerase chain reaction. Clin Invest Med. 2011;34(4):E238.PubMedCrossRef
75.
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(2):271–6.PubMedCrossRef
76.
Piciocchi M, Cardin R, Vitale A, Vanin V, Giacomin A, Pozzan C, Maddalo G, Cillo U, Guido M, Farinati F. Circulating free DNA in the progression of liver damage to hepatocellular carcinoma. Hepatol Int. 2013;7(4):1050–7.PubMedCrossRef
77.
Huang A, Zhang X, Zhou SL, Cao Y, Huang XW, Fan J, Yang XR, Zhou J. Plasma circulating cell-free DNA integrity as a promising biomarker for diagnosis and surveillance in patients with hepatocellular carcinoma. J Cancer. 2016;7(13):1798–803.PubMedPubMedCentralCrossRef
78.
Yan L, Chen Y, Zhou J, Zhao H, Zhang H, Wang G. Diagnostic value of circulating cell-free DNA levels for hepatocellular carcinoma. Int J Infect Dis. 2017;67:92–7.PubMedCrossRef
79.
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(9):3516–21.PubMed
80.
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(8):2378–84.PubMedCrossRef
81.
Iyer P, Zekri AR, Hung CW, Schiefelbein E, Ismail K, Hablas A, Seifeldin IA, Soliman AS. Concordance of DNA methylation pattern in plasma and tumor DNA of Egyptian hepatocellular carcinoma patients. Exp Mol Pathol. 2010;88(1):107–11.PubMedCrossRef
82.
Iizuka N, Oka M, Sakaida I, Moribe T, Miura T, Kimura N, Tamatsukuri S, Ishitsuka H, Uchida K, Terai S, et al. Efficient detection of hepatocellular carcinoma by a hybrid blood test of epigenetic and classical protein markers. Clin Chim Acta. 2011;412(1–2):152–8.PubMedCrossRef
83.
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(3):702–7.PubMedCrossRef
84.
Wong IH, Zhang J, Lai PB, Lau WY, Lo YM. Quantitative analysis of tumor-derived methylated p16INK4a sequences in plasma, serum, and blood cells of hepatocellular carcinoma patients. Clin Cancer Res. 2003;9(3):1047–52.PubMed
85.
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(4):1010–5.PubMedCrossRef
86.
Chang H, Yi B, Li L, Zhang HY, Sun F, Dong SQ, Cao Y. Methylation of tumor associated genes in tissue and plasma samples from liver disease patients. Exp Mol Pathol. 2008;85(2):96–100.PubMedCrossRef
87.
Yeo W, Wong N, Wong WL, Lai PB, Zhong S, Johnson PJ. High frequency of promoter hypermethylation of RASSF1A in tumor and plasma of patients with hepatocellular carcinoma. Liver Int. 2005;25(2):266–72.PubMedCrossRef
88.
Chan KC, Lai PB, Mok TS, Chan HL, Ding C, Yeung SW, Lo YM. Quantitative analysis of circulating methylated DNA as a biomarker for hepatocellular carcinoma. Clin Chem. 2008;54(9):1528–36.PubMedCrossRef
89.
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(3):111–5.PubMedCrossRef
90.
Zhang P, Wen X, Gu F, Deng X, Li J, Dong J, Jiao J, Tian Y. Methylation profiling of serum DNA from hepatocellular carcinoma patients using an Infinium human methylation 450 BeadChip. Hepatol Int. 2013;7(3):893–900.PubMedCrossRef
91.
Han LY, Fan YC, Mu NN, Gao S, Li F, Ji XF, Dou CY, Wang K. Aberrant DNA methylation of G-protein-coupled bile acid receptor Gpbar1 (TGR5) is a potential biomarker for hepatitis B virus associated hepatocellular carcinoma. Int J Med Sci. 2014;11(2):164–71.PubMedPubMedCentralCrossRef
92.
Ji XF, Fan YC, Gao S, Yang Y, Zhang JJ, Wang K. MT1M and MT1G promoter methylation as biomarkers for hepatocellular carcinoma. World J Gastroenterol. 2014;20(16):4723–9.PubMedPubMedCentralCrossRef
93.
Huang G, Krocker JD, Kirk JL, Merwat SN, Ju H, Soloway RD, Wieck LR, Li A, Okorodudu AO, Petersen JR, et al. Evaluation of INK4A promoter methylation using pyrosequencing and circulating cell-free DNA from patients with hepatocellular carcinoma. Clin Chem Lab Med. 2014;52(6):899–909.PubMedPubMedCentralCrossRef
94.
Xu RH, Wei W, Krawczyk M, Wang W, Luo H, Flagg K, Yi S, Shi W, Quan Q, Li K, et al. Circulating tumour DNA methylation markers for diagnosis and prognosis of hepatocellular carcinoma. Nat Mater. 2017;16(11):1155–61.PubMedCrossRef
95.
Yu L, Liu X, Han C, Lu S, Zhu G, Su H, Qi W, Liao X, Peng T. 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(8):765–74.PubMedCrossRef
96.
Huang A, Zhao X, Yang XR, Li FQ, Zhou XL, Wu K, Zhang X, Sun QM, Cao Y, Zhu HM, et al. Circumventing intratumoral heterogeneity to identify potential therapeutic targets in hepatocellular carcinoma. J Hepatol. 2017;67(2):293–301.PubMedCrossRef
97.
Cai ZX, Chen G, Zeng YY, Dong XQ, Lin MJ, Huang XH, Zhang D, Liu XL, Liu JF. Circulating tumor DNA profiling reveals clonal evolution and real-time disease progression in advanced hepatocellular carcinoma. Int J Cancer. 2017;141(5):977–85.PubMedCrossRef
98.
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(13):1907–14.PubMedPubMedCentralCrossRef
99.
Jiang P, Chan CW, Chan KC, Cheng SH, Wong J, Wong VW, Wong GL, Chan SL, Mok TS, Chan HL, et al. Lengthening and shortening of plasma DNA in hepatocellular carcinoma patients. Proc Natl Acad Sci U S A. 2015;112(11):E1317–25.PubMedPubMedCentralCrossRef
100.
Chang Y, Tolani B, Nie X, Zhi X, Hu M, He B. Review of the clinical applications and technological advances of circulating tumor DNA in cancer monitoring. Ther Clin Risk Manag. 2017;13:1363–74.PubMedPubMedCentralCrossRef
101.
Bruix J, Qin S, Merle P, Granito A, Huang YH, Bodoky G, Pracht M, Yokosuka O, Rosmorduc O, Breder V, 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(10064):56–66.PubMedCrossRef
102.
Prieto J, Melero I, Sangro B. Immunological landscape and immunotherapy of hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol. 2015;12(12):681–700.PubMedCrossRef
103.
Funaki N, Tanaka J, Seto S, Kasamatsu T, Kaido T, Imamura M. Highly-sensitive identification of alpha-fetoprotein mRNA in circulating peripheral blood of hepatocellular carcinoma patients. Life Sci. 1995;57(17):1621–31.PubMedCrossRef
104.
Vona G, Estepa L, Beroud C, Damotte D, Capron F, Nalpas B, Mineur A, Franco D, Lacour B, Pol S, et al. Impact of cytomorphological detection of circulating tumor cells in patients with liver cancer. Hepatology. 2004;39(3):792–7.PubMedCrossRef
105.
Chen T, Xie G, Wang X, Fan J, Qiu Y, Zheng X, Qi X, Cao Y, Su M, Wang X, et al. Serum and urine metabolite profiling reveals potential biomarkers of human hepatocellular carcinoma. Mol Cell Proteomics. 2011;10(7):M110 004945.PubMedPubMedCentralCrossRef
106.
Mu H, Lin KX, Zhao H, Xing S, Li C, Liu F, Lu HZ, Zhang Z, Sun YL, Yan XY, et al. Identification of biomarkers for hepatocellular carcinoma by semiquantitative immunocytochemistry. World J Gastroenterol. 2014;20(19):5826–38.PubMedPubMedCentralCrossRef
107.
Guo W, Yang XR, Sun YF, Shen MN, Ma XL, Wu J, Zhang CY, Zhou Y, Xu Y, Hu B, et al. 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(18):4794–805.PubMedCrossRef
108.
Zhou Y, Wang B, Wu J, Zhang C, Zhou Y, Yang X, Zhou J, Guo W, Fan J. Association of preoperative EpCAM circulating tumor cells and peripheral Treg cell levels with early recurrence of hepatocellular carcinoma following radical hepatic resection. BMC Cancer. 2016;16:506.PubMedPubMedCentralCrossRef
109.
von Felden J, Schulze K, Krech T, Ewald F, Nashan B, Pantel K, Lohse AW, Riethdorf S, Wege H. Circulating tumor cells as liquid biomarker for high HCC recurrence risk after curative liver resection. Oncotarget. 2017;8(52):89978–87.PubMedPubMedCentralCrossRef
Metadata
Title
Clinical applications of liquid biopsy as prognostic and predictive biomarkers in hepatocellular carcinoma: circulating tumor cells and circulating tumor DNA
Authors
Jie Li
Xu Han
Xiaona Yu
Zongzhen Xu
Guangsheng Yang
Bingqi Liu
Peng Xiu
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2018
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-018-0893-1

Other articles of this Issue 1/2018

Journal of Experimental & Clinical Cancer Research 1/2018 Go to the issue

Research

Hypermethylation of DMTN promotes the metastasis of colorectal cancer cells by regulating the actin cytoskeleton through Rac1 signaling activation

Research

Circular RNA IARS (circ-IARS) secreted by pancreatic cancer cells and located within exosomes regulates endothelial monolayer permeability to promote tumor metastasis

Research

Co-occurring KRAS mutation/LKB1 loss in non-small cell lung cancer cells results in enhanced metabolic activity susceptible to caloric restriction: an in vitro integrated multilevel approach

Research

Downregulation of miR-133a-3p promotes prostate cancer bone metastasis via activating PI3K/AKT signaling

Research

The CXCL5/CXCR2 axis contributes to the epithelial-mesenchymal transition of nasopharyngeal carcinoma cells by activating ERK/GSK-3β/snail signalling

Research

17β-estradiol upregulates IL6 expression through the ERβ pathway to promote lung adenocarcinoma progression
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits