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Current Medicinal Chemistry

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ISSN (Online): 1875-533X

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Systematic Review Article

Detection of Circulating Cell-free DNA to Diagnose Hepatocellular Carcinoma in Chinese Population: A Systematic Review and Meta-analysis

Author(s): Amir Hossein Aalami*, Farnoosh Aalami, Ehsan Kargar Aliabadi, Amir Amirabadi and Amirhossein Sahebkar*

Volume 31, Issue 22, 2024

Published on: 12 September, 2023

Page: [3345 - 3359] Pages: 15

DOI: 10.2174/0929867330666230622114235

Price: $65

Abstract

Background: Cell-free circulating DNA has been known for many years, but this knowledge has not been beneficial for diagnosis. In this meta-analysis, we examine the diagnostic role of circulating cell-free DNA in HCC patients to find a reliable biomarker for the early detection of HCC.

Materials and Methods: We performed a systematic literature search using Science Direct, Web of Science, PubMed/Medline, Scopus, Google Scholar, and Embase, up to April 1st, 2022. Meta-Disc V.1.4 and Comprehensive Meta-Analysis V.3.3 software calculated the pooled specificity, sensitivity, area under the curve (AUC), diagnostic odds ratio (DOR), positive likelihood ratio (PLR), negative likelihood ratio (NLR) Q*index, and summary receiver-- operating characteristic (SROC) for the role of cfDNA as a biomarker for HCC patients. Moreover, the subgroup analyses have been performed based on sample types (serum/plasma) and detection methods (MS-PCR/methylation).

Results: A total of 7 articles (9 studies) included 697 participants (485 cases and 212 controls). The overall pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were 0.706 (95% CI: 0.671 - 0.739), 0.905 (95% CI: 0.865 - 0.937), 6.66 (95% CI: 4.36 - 10.18), 0.287 (95% CI: 0.185 - 0.445), 28.40 (95% CI: 13.01 - 62.0), and 0.93, respectively. We conducted a subgroup analysis of diagnostic value, which showed that the plasma sample had a better diagnostic value compared to the serum.

Conclusion: This meta-analysis showed that cfDNA could be a fair biomarker for diagnosing HCC patients.

« Previous Next »
[1]
Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2021, 71(3), 209-249.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[2]
McGlynn, K.A.; Petrick, J.L.; El-Serag, H.B. Epidemiology of hepatocellular carcinoma. Hepatology, 2021, 73(S1)(Suppl. 1), 4-13.
[http://dx.doi.org/10.1002/hep.31288] [PMID: 32319693]
[3]
Petrick, J.L.; Florio, A.A.; Znaor, A.; Ruggieri, D.; Laversanne, M.; Alvarez, C.S.; Ferlay, J.; Valery, P.C.; Bray, F.; McGlynn, K.A. International trends in hepatocellular carcinoma incidence, 1978–2012. Int. J. Cancer, 2020, 147(2), 317-330.
[http://dx.doi.org/10.1002/ijc.32723] [PMID: 31597196]
[4]
Llovet, J.M.; Kelley, R.K.; Villanueva, A.; Singal, A.G.; Pikarsky, E.; Roayaie, S.; Lencioni, R.; Koike, K.; Zucman-Rossi, J.; Finn, R.S. Hepatocellular carcinoma. Nat. Rev. Dis. Primers, 2021, 7(1), 6.
[http://dx.doi.org/10.1038/s41572-020-00240-3] [PMID: 33479224]
[5]
Mirzaei H.; Sahebkar A.; Jaafari M.R.; Goodarzi M.; Mirzaei H.R. Diagnostic and therapeutic potential of exosomes in cancer: The beginning of a new tale? J. Cell. Physiol.2017, 232(12), 3251-3260.
[http://dx.doi.org/10.1002/jcp.25739]
[6]
Sahebkar, A.; Aalami, A.H.; Aalami, F. Gastric cancer and circulating microRNAs: An updated systematic review and diagnostic meta-analysis. Curr. Med. Chem., 2023, 30(33), 3798-3814.
[http://dx.doi.org/10.2174/0929867330666221121155905] [PMID: 36411580]
[7]
Aalami, A.H.; Hoseinzadeh, M.; Hosseini Manesh, P.; Jiryai Sharahi, A.; Kargar Aliabadi, E. Carcinogenic effects of heavy metals by inducing dysregulation of microRNAs: A review. Mol. Biol. Rep., 2022, 49(12), 12227-12238.
[http://dx.doi.org/10.1007/s11033-022-07897-x] [PMID: 36269534]
[8]
Aalami, A.H.; Abdeahad, H.; Shoghi, A.; Mesgari, M.; Amirabadi, A.; Sahebkar, A. Brain tumors and circulating micrornas: A systematic review and diagnostic meta-analysis. Expert Rev. Mol. Diagn., 2022, 22(2), 201-211.
[http://dx.doi.org/10.1080/14737159.2022.2019016] [PMID: 34906021]
[9]
Aalami, A.H.; Abdeahad, H.; Aalami, F.; Amirabadi, A. Can microRNAs be utilized as tumor markers for recurrence following nephrectomy in renal cell carcinoma patients? A meta-analysis provides the answer. Urol. Oncol., 2023, 41(1), 52.e1-52.e10.
[10]
Qasemi Rad, M.; Pouresmaeil, V.; Hosseini Mojahed, F.; Amirabadi, A.; Aalami, A.H. Clinicopathological utility of miR-203a-3p in diagnosing colorectal cancer. Mol. Biol. Rep., 2022, 49(7), 6975-6985.
[http://dx.doi.org/10.1007/s11033-022-07465-3] [PMID: 35511316]
[11]
Han, D.S.C.; Lo, Y.M.D. The nexus of cfDNA and nuclease biology. Trends Genet., 2021, 37(8), 758-770.
[http://dx.doi.org/10.1016/j.tig.2021.04.005] [PMID: 34006390]
[12]
Moss, J.; Magenheim, J.; Neiman, D.; Zemmour, H.; Loyfer, N.; Korach, A.; Samet, Y.; Maoz, M.; Druid, H.; Arner, P.; Fu, K.Y.; Kiss, E.; Spalding, K.L.; Landesberg, G.; Zick, A.; Grinshpun, A.; Shapiro, A.M.J.; Grompe, M.; Wittenberg, A.D.; Glaser, B.; Shemer, R.; Kaplan, T.; Dor, Y. Comprehensive human cell-type methylation atlas reveals origins of circulating cell-free DNA in health and disease. Nat. Commun., 2018, 9(1), 5068.
[http://dx.doi.org/10.1038/s41467-018-07466-6] [PMID: 30498206]
[13]
Daraghmeh, D.N.; King, C.; Wiese, M.D. A review of liquid biopsy as a tool to assess epigenetic, cfDNA and miRNA variability as methotrexate response predictors in patients with rheumatoid arthritis. Pharmacol. Res., 2021, 173, 105887.
[http://dx.doi.org/10.1016/j.phrs.2021.105887] [PMID: 34536550]
[14]
Meddeb, R.; Dache, Z.A.A.; Thezenas, S.; Otandault, A.; Tanos, R.; Pastor, B.; Sanchez, C.; Azzi, J.; Tousch, G.; Azan, S.; Mollevi, C.; Adenis, A.; El Messaoudi, S.; Blache, P.; Thierry, A.R. Quantifying circulating cell-free DNA in humans. Sci. Rep., 2019, 9(1), 5220.
[http://dx.doi.org/10.1038/s41598-019-41593-4] [PMID: 30914716]
[15]
Alborelli, I.; Generali, D.; Jermann, P.; Cappelletti, M.R.; Ferrero, G.; Scaggiante, B.; Bortul, M.; Zanconati, F.; Nicolet, S.; Haegele, J.; Bubendorf, L.; Aceto, N.; Scaltriti, M.; Mucci, G.; Quagliata, L.; Novelli, G. Cell-free DNA analysis in healthy individuals by next-generation sequencing: A proof of concept and technical validation study. Cell Death Dis., 2019, 10(7), 534.
[http://dx.doi.org/10.1038/s41419-019-1770-3] [PMID: 31296838]
[16]
Heitzer, E.; Haque, I.S.; Roberts, C.E.S.; Speicher, M.R. Current and future perspectives of liquid biopsies in genomics-driven oncology. Nat. Rev. Genet., 2019, 20(2), 71-88.
[http://dx.doi.org/10.1038/s41576-018-0071-5] [PMID: 30410101]
[17]
Liu, M.C.; Oxnard, G.R.; Klein, E.A.; Swanton, C.; Seiden, M.V.; Liu, M.C.; Oxnard, G.R.; Klein, E.A.; Smith, D.; Richards, D.; Yeatman, T.J.; Cohn, A.L.; Lapham, R.; Clement, J.; Parker, A.S.; Tummala, M.K.; McIntyre, K.; Sekeres, M.A.; Bryce, A.H.; Siegel, R.; Wang, X.; Cosgrove, D.P.; Abu-Rustum, N.R.; Trent, J.; Thiel, D.D.; Becerra, C.; Agrawal, M.; Garbo, L.E.; Giguere, J.K.; Michels, R.M.; Harris, R.P.; Richey, S.L.; McCarthy, T.A.; Waterhouse, D.M.; Couch, F.J.; Wilks, S.T.; Krie, A.K.; Balaraman, R.; Restrepo, A.; Meshad, M.W.; Rieger-Christ, K.; Sullivan, T.; Lee, C.M.; Greenwald, D.R.; Oh, W.; Tsao, C-K.; Fleshner, N.; Kennecke, H.F.; Khalil, M.F.; Spigel, D.R.; Manhas, A.P.; Ulrich, B.K.; Kovoor, P.A.; Stokoe, C.; Courtright, J.G.; Yimer, H.A.; Larson, T.G.; Swanton, C.; Seiden, M.V.; Cummings, S.R.; Absalan, F.; Alexander, G.; Allen, B.; Amini, H.; Aravanis, A.M.; Bagaria, S.; Bazargan, L.; Beausang, J.F.; Berman, J.; Betts, C.; Blocker, A.; Bredno, J.; Calef, R.; Cann, G.; Carter, J.; Chang, C.; Chawla, H.; Chen, X.; Chien, T.C.; Civello, D.; Davydov, K.; Demas, V.; Desai, M.; Dong, Z.; Fayzullina, S.; Fields, A.P.; Filippova, D.; Freese, P.; Fung, E.T.; Gnerre, S.; Gross, S.; Halks-Miller, M.; Hall, M.P.; Hartman, A-R.; Hou, C.; Hubbell, E.; Hunkapiller, N.; Jagadeesh, K.; Jamshidi, A.; Jiang, R.; Jung, B.; Kim, T.H.; Klausner, R.D.; Kurtzman, K.N.; Lee, M.; Lin, W.; Lipson, J.; Liu, H.; Liu, Q.; Lopatin, M.; Maddala, T.; Maher, M.C.; Melton, C.; Mich, A.; Nautiyal, S.; Newman, J.; Newman, J.; Nicula, V.; Nicolaou, C.; Nikolic, O.; Pan, W.; Patel, S.; Prins, S.A.; Rava, R.; Ronaghi, N.; Sakarya, O.; Satya, R.V.; Schellenberger, J.; Scott, E.; Sehnert, A.J.; Shaknovich, R.; Shanmugam, A.; Shashidhar, K.C.; Shen, L.; Shenoy, A.; Shojaee, S.; Singh, P.; Steffen, K.K.; Tang, S.; Toung, J.M.; Valouev, A.; Venn, O.; Williams, R.T.; Wu, T.; Xu, H.H.; Yakym, C.; Yang, X.; Yecies, J.; Yip, A.S.; Youngren, J.; Yue, J.; Zhang, J.; Zhang, L.; Zhang, L.Q.; Zhang, N.; Curtis, C.; Berry, D.A. Sensitive and specific multi-cancer detection and localization using methylation signatures in cell-free DNA. Ann. Oncol., 2020, 31(6), 745-759.
[http://dx.doi.org/10.1016/j.annonc.2020.02.011] [PMID: 33506766]
[18]
Fang, Y.S.; Wu, Q.; Zhao, H.C.; Zhou, Y.; Ye, L.; Liu, S.S.; Li, X.X.; Du, W.D. Do combined assays of serum AFP, AFP-L3, DCP, GP73, and DKK-1 efficiently improve the clinical values of biomarkers in decision-making for hepatocellular carcinoma? A meta-analysis. Expert Rev. Gastroenterol. Hepatol., 2021, 15(9), 1065-1076.
[http://dx.doi.org/10.1080/17474124.2021.1900731] [PMID: 33691550]
[19]
Qi, F.; Zhou, A.; Yan, L.; Yuan, X.; Wang, D.; Chang, R.; Zhang, Y.; Shi, F.; Han, X.; Hou, J.; Wei, L.; Zhang, X. The diagnostic value of PIVKA-II, AFP, AFP-L3, CEA, and their combinations in primary and metastatic hepatocellular carcinoma. J. Clin. Lab. Anal., 2020, 34(5), e23158.
[http://dx.doi.org/10.1002/jcla.23158] [PMID: 31821607]
[20]
Piñero, F.; Dirchwolf, M.; Pessôa, M.G. Biomarkers in hepatocellular carcinoma: Diagnosis, prognosis and treatment response assessment. Cells, 2020, 9(6), 1370.
[http://dx.doi.org/10.3390/cells9061370] [PMID: 32492896]
[21]
de Lima, L.T.F.; Broszczak, D.; Zhang, X.; Bridle, K.; Crawford, D.; Punyadeera, C. The use of minimally invasive biomarkers for the diagnosis and prognosis of hepatocellular carcinoma. Biochim Biophys Acta Rev Cancer, 2020, 1874(2), 188451.
[http://dx.doi.org/10.1016/j.bbcan.2020.188451] [PMID: 33065194]
[22]
Wang, Y.; Wang, Y.; Huang, A.; Jiang, R.; Zheng, J.; Li, Z. The genetic and epigenetic abnormalities of plasma cfDNA as liquid biopsy biomarkers to diagnose hepatocellular carcinoma; AACR, 2020.
[http://dx.doi.org/10.1158/1538-7445.AM2020-782]
[23]
Page, M.J.; McKenzie, J.E.; Bossuyt, P.M.; Boutron, I.; Hoffmann, T.C.; Mulrow, C.D.; Shamseer, L.; Tetzlaff, J.M.; Moher, D. Updating guidance for reporting systematic reviews: Development of the PRISMA 2020 statement. J. Clin. Epidemiol., 2021, 134, 103-112.
[http://dx.doi.org/10.1016/j.jclinepi.2021.02.003] [PMID: 33577987]
[24]
Moses, L.E.; Shapiro, D.; Littenberg, B. Combining independent studies of a diagnostic test into a summary roc curve: Data-analytic approaches and some additional considerations. Stat. Med., 1993, 12(14), 1293-1316.
[http://dx.doi.org/10.1002/sim.4780121403] [PMID: 8210827]
[25]
Furuya-Kanamori, L.; Kostoulas, P.; Doi, S.A.R. A new method for synthesizing test accuracy data outperformed the bivariate method. J. Clin. Epidemiol., 2021, 132, 51-58.
[http://dx.doi.org/10.1016/j.jclinepi.2020.12.015] [PMID: 33333166]
[26]
Sha, Y.S.; Chen, J.F. MRI-based radiomics for the diagnosis of triple-negative breast cancer: A meta-analysis. Clin. Radiol., 2022, 77(9), 655-663.
[http://dx.doi.org/10.1016/j.crad.2022.04.015] [PMID: 35641339]
[27]
Zeng, Q-S; Zhao, Z-J; Nie, J; Zou, M; Yang, J-H; Zhang, J-Z Efficacy and safety of endoscopic submucosal dissection for dysplasia in ulcerative colitis patients: A systematic review and meta-analysis. Gastroenterol Res Pract, 2022, 2022, 9556161.
[http://dx.doi.org/10.1155/2022/9556161] [PMID: 35126511]
[28]
Sedgwick, P. Spearman's rank correlation coefficient. BMJ, 2014, 349, g7327.
[http://dx.doi.org/10.1136/bmj.g7327]
[29]
Akoglu, H. User’s guide to correlation coefficients. Turk. J. Emerg. Med., 2018, 18(3), 91-93.
[http://dx.doi.org/10.1016/j.tjem.2018.08.001] [PMID: 30191186]
[30]
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), 271-276.
[http://dx.doi.org/10.1007/s12253-011-9438-z] [PMID: 21779787]
[31]
Huang, A.; Zhang, X.; Zhou, S.L.; Cao, Y.; Huang, X.W.; Fan, J.; Yang, X.R.; 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), 1798-1803.
[http://dx.doi.org/10.7150/jca.15618] [PMID: 27698918]
[32]
Sun, F.K.; Fan, Y.C.; Zhao, J.; Zhang, F.; Gao, S.; Zhao, Z.H.; Sun, Q.; Wang, K. Detection of TFPI2 methylation in the serum of hepatocellular carcinoma patients. Dig. Dis. Sci., 2013, 58(4), 1010-1015.
[http://dx.doi.org/10.1007/s10620-012-2462-3] [PMID: 23108564]
[33]
Chan, K.C.A.; Lai, P.B.S.; Mok, T.S.K.; Chan, H.L.Y.; Ding, C.; Yeung, S.W.; Lo, Y.M.D. Quantitative analysis of circulating methylated DNA as a biomarker for hepatocellular carcinoma. Clin. Chem., 2008, 54(9), 1528-1536.
[http://dx.doi.org/10.1373/clinchem.2008.104653] [PMID: 18653827]
[34]
Ji, X.F.; Fan, Y-C.; Gao, S.; Yang, Y.; Zhang, J-J.; Wang, K. MT1M and MT1G promoter methylation as biomarkers for hepatocellular carcinoma. World J. Gastroenterol., 2014, 20(16), 4723-4729.
[http://dx.doi.org/10.3748/wjg.v20.i16.4723] [PMID: 24782625]
[35]
Zhang, Y.J.; Wu, H.C.; Shen, J.; Ahsan, H.; Tsai, W.Y.; Yang, H.I.; Wang, L.Y.; Chen, S.Y.; Chen, C.J.; Santella, R.M. Predicting hepatocellular carcinoma by detection of aberrant promoter methylation in serum DNA. Clin. Cancer Res., 2007, 13(8), 2378-2384.
[http://dx.doi.org/10.1158/1078-0432.CCR-06-1900] [PMID: 17438096]
[36]
Jiang, P.; Chan, C.W.M.; Chan, K.C.A.; Cheng, S.H.; Wong, J.; Wong, V.W.S.; Wong, G.L.H.; Chan, S.L.; Mok, T.S.K.; Chan, H.L.Y.; Lai, P.B.S.; Chiu, R.W.K.; Lo, Y.M.D. Lengthening and shortening of plasma DNA in hepatocellular carcinoma patients. Proc. Natl. Acad. Sci. USA, 2015, 112(11), E1317-E1325.
[http://dx.doi.org/10.1073/pnas.1500076112] [PMID: 25646427]
[37]
Ranganathan, P.; Aggarwal, R. Understanding the properties of diagnostic tests-Part 2: Likelihood ratios. Perspect. Clin. Res., 2018, 9(2), 99-102.
[http://dx.doi.org/10.4103/picr.PICR_41_18] [PMID: 29862204]
[38]
Jones, C.M.; Athanasiou, T. Summary receiver operating characteristic curve analysis techniques in the evaluation of diagnostic tests. Ann. Thorac. Surg., 2005, 79(1), 16-20.
[http://dx.doi.org/10.1016/j.athoracsur.2004.09.040] [PMID: 15620907]
[39]
Park, H.J.; Jang, H.Y.; Kim, S.Y.; Lee, S.J.; Won, H.J.; Byun, J.H.; Choi, S.H.; Lee, S.S.; An, J.; Lim, Y.S. Non-enhanced magnetic resonance imaging as a surveillance tool for hepatocellular carcinoma: Comparison with ultrasound. J. Hepatol., 2020, 72(4), 718-724.
[http://dx.doi.org/10.1016/j.jhep.2019.12.001] [PMID: 31836549]
[40]
Li, B; Huang, H; Huang, R SEPT9 gene methylation as a noninvasive marker for hepatocellular carcinoma. Dis Markers, 2020, 2020, 6289063.
[http://dx.doi.org/10.1155/2020/6289063] [PMID: 33178361]
[41]
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., 2018, 67, 92-97.
[http://dx.doi.org/10.1016/j.ijid.2017.12.002] [PMID: 29229500]
[42]
Howell, J.; Atkinson, S.R.; Pinato, D.J.; Knapp, S.; Ward, C.; Minisini, R.; Burlone, M.E.; Leutner, M.; Pirisi, M.; Büttner, R.; Khan, S.A.; Thursz, M.; Odenthal, M.; Sharma, R. Identification of mutations in circulating cell-free tumour DNA as a biomarker in hepatocellular carcinoma. Eur. J. Cancer, 2019, 116, 56-66.
[http://dx.doi.org/10.1016/j.ejca.2019.04.014] [PMID: 31173963]
[43]
Pezzuto, F.; Buonaguro, L.; Buonaguro, F.; Tornesello, M. The role of circulating free DNA and microRNA in non-invasive diagnosis of HBV-and HCV-related hepatocellular carcinoma. Int. J. Mol. Sci., 2018, 19(4), 1007.
[http://dx.doi.org/10.3390/ijms19041007] [PMID: 29597259]
[44]
Ma, K.; Liu, J.; Wang, Y.; Zhong, Y.; Wu, Z.; Fan, R.; Guo, S. Relationship between plasma cell-free DNA (cfDNA) and prognosis of TACE for primary hepatocellular carcinoma. J. Gastrointest. Oncol., 2020, 11(6), 1350-1363.
[http://dx.doi.org/10.21037/jgo-20-509] [PMID: 33457006]
[45]
Ren, N.; Ye, Q-H.; Qin, L-X.; Zhang, B-H.; Liu, Y-K.; Tang, Z-Y. Circulating DNA level is negatively associated with the long-term survival of hepatocellular carcinoma patients. World J. Gastroenterol., 2006, 12(24), 3911-3914.
[http://dx.doi.org/10.3748/wjg.v12.i24.3911] [PMID: 16804981]
[46]
Nakatsuka, T.; Nakagawa, H.; Hayata, Y.; Wake, T.; Yamada, T.; Nishibatake Kinoshita, M.; Nakagomi, R.; Sato, M.; Minami, T.; Uchino, K.; Enooku, K.; Kudo, Y.; Tanaka, Y.; Kishikawa, T.; Otsuka, M.; Tateishi, R.; Koike, K. Post-treatment cell-free DNA as a predictive biomarker in molecular-targeted therapy of hepatocellular carcinoma. J. Gastroenterol., 2021, 56(5), 456-469.
[http://dx.doi.org/10.1007/s00535-021-01773-4] [PMID: 33712873]
[47]
Coto-Llerena, M.; Terracciano, L.M.; von Flüe, M.; Ng, C.K.; Piscuoglio, S. Cell-free DNA in hepatocellular carcinoma. Precision medicine for investigators, practitioners and providers; Elsevier, 2020, pp. 199-209.
[http://dx.doi.org/10.1016/B978-0-12-819178-1.00019-8]
[48]
Chen, W.; Tang, D.; Tang, D.; Dai, Y. Epigenetic silencing of ZIC4 contributes to cancer progression in hepatocellular carcinoma. Cell Death Dis., 2020, 11(10), 906.
[http://dx.doi.org/10.1038/s41419-020-03109-1] [PMID: 33097694]
[49]
Xu, G.; Zhou, X.; Xing, J.; Xiao, Y.; Jin, B.; Sun, L.; Yang, H.; Du, S.; Xu, H.; Mao, Y. Identification of RASSF1A promoter hypermethylation as a biomarker for hepatocellular carcinoma. Cancer Cell Int., 2020, 20(1), 547.
[http://dx.doi.org/10.1186/s12935-020-01638-5] [PMID: 33292241]
[50]
Cozma, A.; Fodor, A.; Vulturar, R.; Sitar-Tăut, A.V.; Orăşan, O.H.; Mureşan, F.; Login, C.; Suharoschi, R. DNA methylation and micro-RNAs: the most recent and relevant biomarkers in the early diagnosis of hepatocellular carcinoma. Medicina (Kaunas), 2019, 55(9), 607.
[http://dx.doi.org/10.3390/medicina55090607] [PMID: 31546948]
[51]
Mohamed, N.A.; Swify, E.M.; Amin, N.F.; Soliman, M.M.; Tag-Eldin, L.M.; Elsherbiny, N.M. Is serum level of methylated RASSF1A valuable in diagnosing hepatocellular carcinoma in patients with chronic viral hepatitis C? Arab J. Gastroenterol., 2012, 13(3), 111-115.
[http://dx.doi.org/10.1016/j.ajg.2012.06.009] [PMID: 23122451]
[52]
Zhang, J.; Yuan, Y.; Gao, S.; Zhao, X.; Li, H. Diagnostic performance of circulating cell-free DNA for hepatocellular carcinoma: a systematic review and meta-analysis. Biomarkers Med., 2021, 15(3), 219-239.
[http://dx.doi.org/10.2217/bmm-2020-0334] [PMID: 33470842]

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