Detection of Circulating Cell-free DNA to Diagnose Hepatocellular Carcinoma in Chinese Population: A Systematic Review and Meta-analysis
- 作者: Aalami A.1, Aalami F.2, Aliabadi E.3, Amirabadi A.4, Sahebkar A.5
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隶属关系:
- Department of Nutrition and Integrative Physiology, College of Health, University of Utah
- Student Research Committee, Faculty of Medicine, North Khorasan University of Medical Sciences
- Department of Chemistry, Faculty of Science, Biochemical Research Center,, Ferdowsi University of Mashhad
- Department of Internal Medicine, Faculty of Medicine, Mashhad Medical Sciences, Islamic Azad University
- Applied Biomedical Research Center, Mashhad University of Medical Sciences
- 期: 卷 31, 编号 22 (2024)
- 页面: 3345-3359
- 栏目: Anti-Infectives and Infectious Diseases
- URL: https://medjrf.com/0929-8673/article/view/644770
- DOI: https://doi.org/10.2174/0929867330666230622114235
- ID: 644770
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详细
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.
作者简介
Amir Aalami
Department of Nutrition and Integrative Physiology, College of Health, University of Utah
编辑信件的主要联系方式.
Email: info@benthamscience.net
Farnoosh Aalami
Student Research Committee, Faculty of Medicine, North Khorasan University of Medical Sciences
Email: info@benthamscience.net
Ehsan Aliabadi
Department of Chemistry, Faculty of Science, Biochemical Research Center,, Ferdowsi University of Mashhad
Email: info@benthamscience.net
Amir Amirabadi
Department of Internal Medicine, Faculty of Medicine, Mashhad Medical Sciences, Islamic Azad University
Email: info@benthamscience.net
Amirhossein Sahebkar
Applied Biomedical Research Center, Mashhad University of Medical Sciences
编辑信件的主要联系方式.
Email: info@benthamscience.net
参考
- 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. doi: 10.3322/caac.21660 PMID: 33538338
- McGlynn, K.A.; Petrick, J.L.; El-Serag, H.B. Epidemiology of hepatocellular carcinoma. Hepatology, 2021, 73(S1)(Suppl. 1), 4-13. doi: 10.1002/hep.31288 PMID: 32319693
- 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, 19782012. Int. J. Cancer, 2020, 147(2), 317-330. doi: 10.1002/ijc.32723 PMID: 31597196
- 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. doi: 10.1038/s41572-020-00240-3 PMID: 33479224
- 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. doi: 10.1002/jcp.25739
- 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. doi: 10.2174/0929867330666221121155905 PMID: 36411580
- 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. doi: 10.1007/s11033-022-07897-x PMID: 36269534
- 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. doi: 10.1080/14737159.2022.2019016 PMID: 34906021
- 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.
- 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. doi: 10.1007/s11033-022-07465-3 PMID: 35511316
- Han, D.S.C.; Lo, Y.M.D. The nexus of cfDNA and nuclease biology. Trends Genet., 2021, 37(8), 758-770. doi: 10.1016/j.tig.2021.04.005 PMID: 34006390
- 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. doi: 10.1038/s41467-018-07466-6 PMID: 30498206
- 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. doi: 10.1016/j.phrs.2021.105887 PMID: 34536550
- 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. doi: 10.1038/s41598-019-41593-4 PMID: 30914716
- 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. doi: 10.1038/s41419-019-1770-3 PMID: 31296838
- 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. doi: 10.1038/s41576-018-0071-5 PMID: 30410101
- 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. doi: 10.1016/j.annonc.2020.02.011 PMID: 33506766
- 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. doi: 10.1080/17474124.2021.1900731 PMID: 33691550
- 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. doi: 10.1002/jcla.23158 PMID: 31821607
- Piñero, F.; Dirchwolf, M.; Pessôa, M.G. Biomarkers in hepatocellular carcinoma: Diagnosis, prognosis and treatment response assessment. Cells, 2020, 9(6), 1370. doi: 10.3390/cells9061370 PMID: 32492896
- 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. doi: 10.1016/j.bbcan.2020.188451 PMID: 33065194
- 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. doi: 10.1158/1538-7445.AM2020-782
- 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. doi: 10.1016/j.jclinepi.2021.02.003 PMID: 33577987
- 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. doi: 10.1002/sim.4780121403 PMID: 8210827
- 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. doi: 10.1016/j.jclinepi.2020.12.015 PMID: 33333166
- 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. doi: 10.1016/j.crad.2022.04.015 PMID: 35641339
- 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. doi: 10.1155/2022/9556161 PMID: 35126511
- Sedgwick, P. Spearman's rank correlation coefficient. BMJ, 2014, 349, g7327. doi: 10.1136/bmj.g7327
- Akoglu, H. Users guide to correlation coefficients. Turk. J. Emerg. Med., 2018, 18(3), 91-93. doi: 10.1016/j.tjem.2018.08.001 PMID: 30191186
- 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. doi: 10.1007/s12253-011-9438-z PMID: 21779787
- 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. doi: 10.7150/jca.15618 PMID: 27698918
- 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. doi: 10.1007/s10620-012-2462-3 PMID: 23108564
- 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. doi: 10.1373/clinchem.2008.104653 PMID: 18653827
- 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. doi: 10.3748/wjg.v20.i16.4723 PMID: 24782625
- 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. doi: 10.1158/1078-0432.CCR-06-1900 PMID: 17438096
- 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. doi: 10.1073/pnas.1500076112 PMID: 25646427
- Ranganathan, P.; Aggarwal, R. Understanding the properties of diagnostic tests-Part 2: Likelihood ratios. Perspect. Clin. Res., 2018, 9(2), 99-102. doi: 10.4103/picr.PICR_41_18 PMID: 29862204
- 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. doi: 10.1016/j.athoracsur.2004.09.040 PMID: 15620907
- 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. doi: 10.1016/j.jhep.2019.12.001 PMID: 31836549
- Li, B; Huang, H; Huang, R SEPT9 gene methylation as a noninvasive marker for hepatocellular carcinoma. Dis Markers, 2020, 2020, 6289063. doi: 10.1155/2020/6289063 PMID: 33178361
- 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. doi: 10.1016/j.ijid.2017.12.002 PMID: 29229500
- 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. doi: 10.1016/j.ejca.2019.04.014 PMID: 31173963
- 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. doi: 10.3390/ijms19041007 PMID: 29597259
- 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. doi: 10.21037/jgo-20-509 PMID: 33457006
- 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. doi: 10.3748/wjg.v12.i24.3911 PMID: 16804981
- 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. doi: 10.1007/s00535-021-01773-4 PMID: 33712873
- 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. doi: 10.1016/B978-0-12-819178-1.00019-8
- 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. doi: 10.1038/s41419-020-03109-1 PMID: 33097694
- 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. doi: 10.1186/s12935-020-01638-5 PMID: 33292241
- 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. doi: 10.3390/medicina55090607 PMID: 31546948
- 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. doi: 10.1016/j.ajg.2012.06.009 PMID: 23122451
- 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. doi: 10.2217/bmm-2020-0334 PMID: 33470842
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