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Molecular Biology Reports

, Volume 41, Issue 6, pp 3925–3933 | Cite as

RETRACTED ARTICLE: Role of RASSF1A promoter methylation in the pathogenesis of hepatocellular carcinoma: a meta-analysis of 21 cohort studies

  • Yong-Shuang LiEmail author
  • Qiang Xie
  • Da-Ye Yang
  • Yuan Zheng
Article

Abstract

We carried out the current meta-analysis aiming to comprehensively assess the potential role of RASSF1A aberrant promoter methylation in the pathogenesis of hepatocellular carcinoma (HCC). A range of electronic databases were searched: Web of Science (1945–2013), the Cochrane Library Database (Issue 12, 2013), PubMed (1966–2013), EMBASE (1980–2013), CINAHL (1982–2013) and the Chinese Biomedical Database (CBM) (1982–2013) without language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Crude risk difference (RD) with their 95 % confidence interval (95 % CI) was calculated. In the present meta-analysis, 21 clinical cohort studies with a total of 1,205 HCC patients were included. The results of our meta-analysis illustrated that the frequency of RASSF1A promoter methylation in cancer tissues were significantly higher than those of normal, adjacent and benign tissues (cancer tissues vs. normal tissues: RD = 0.63, 95 % CI 0.53–0.73, P < 0.001; cancer tissues vs. adjacent tissues: RD = 0.43, 95 % CI 0.33–0.53, P < 0.001; cancer tissues vs. benign tissues: RD = 0.48, 95 % CI 038–0.58, P < 0.001; respectively). Further subgroup by ethnicity demonstrated that RASSF1A aberrant promoter methylation was correlated with the pathogenesis of HCC among both Asians and Caucasians (all P < 0.05). The current meta-analysis suggests that RASSF1A aberrant promoter methylation may be implicated in the pathogenesis of HCC. Thus, detection of RASSF1A promoter methylation may be a helpful and valuable biomarker for diagnosis and prognosis of HCC.

Keywords

RASSF1A Promoter methylation Hepatocellular carcinoma Meta-analysis 

Notes

Acknowledgments

We would like to acknowledge the reviewers for their helpful comments on this paper.

Conflict of interest

The authors have declared that no competing interests exist.

References

  1. 1.
    Andersen JB, Factor VM, Marquardt JU, Raggi C, Lee YH, Seo D, Conner EA, Thorgeirsson SS (2010) An integrated genomic and epigenomic approach predicts therapeutic response to zebularine in human liver cancer. Sci Transl Med 2:54ra77. doi: 10.1126/scitranslmed.3001338 PubMedCentralPubMedGoogle Scholar
  2. 2.
    Sherman M (2010) Hepatocellular carcinoma: epidemiology, surveillance, and diagnosis. Semin Liver Dis 30:3–16. doi: 10.1055/s-0030-1247128 CrossRefPubMedGoogle Scholar
  3. 3.
    Chuang SC, La Vecchia C, Boffetta P (2009) Liver cancer: descriptive epidemiology and risk factors other than HBV and HCV infection. Cancer Lett 286:9–14. doi: 10.1016/j.canlet.2008.10.040 CrossRefPubMedGoogle Scholar
  4. 4.
    Pan H, Fu X, Huang W (2011) Molecular mechanism of liver cancer. Anticancer Agents Med Chem 11:493–499. http://www.ncbi.nlm.nih.gov/pubmed/21554201 Google Scholar
  5. 5.
    Arzumanyan A, Reis HM, Feitelson MA (2013) Pathogenic mechanisms in HBV- and HCV-associated hepatocellular carcinoma. Nat Rev Cancer 13:123–135. doi: 10.1038/nrc3449 CrossRefPubMedGoogle Scholar
  6. 6.
    Liu Y, Chang CC, Marsh GM, Wu F (2012) Population attributable risk of aflatoxin-related liver cancer: systematic review and meta-analysis. Eur J Cancer 48:2125–2136. doi: 10.1016/j.ejca.2012.02.009 PubMedCentralCrossRefPubMedGoogle Scholar
  7. 7.
    Zhao ZH, Fan YC, Yang Y, Wang K (2013) Association between Ras association domain family 1A promoter methylation and hepatocellular carcinoma: a meta-analysis. World J Gastroenterol 19:7189–7196. doi: 10.3748/wjg.v19.i41.7189 PubMedCentralCrossRefPubMedGoogle Scholar
  8. 8.
    Dratviman-Storobinsky O, Cohen Y, Frenkel S, Merhavi-Shoham E, El SD, Binkovsky N, Pe’er J, Goldenberg-Cohen N (2012) The role of RASSF1A in uveal melanoma. Invest Ophthalmol Vis Sci 53:2611–2619. doi: 10.1167/iovs.11-7730 CrossRefPubMedGoogle Scholar
  9. 9.
    Duan C, Liu M, Zhang J, Ma R (2013) Rassf1a: a potential novel therapeutic target against cardiac hypertrophy. Prog Biophys Mol Biol 113:284–288. doi: 10.1016/j.pbiomolbio.2013.07.004 CrossRefPubMedGoogle Scholar
  10. 10.
    Yee KS, Grochola L, Hamilton G, Grawenda A, Bond EE, Taubert H, Wurl P, Bond GL et al (2012) A RASSF1A polymorphism restricts p53/p73 activation and associates with poor survival and accelerated age of onset of soft tissue sarcoma. Cancer Res 72:2206–2217. doi: 10.1158/0008-5472.CAN-11-2906 CrossRefPubMedGoogle Scholar
  11. 11.
    Richter AM, Pfeifer GP, Dammann RH (2009) The rassf proteins in cancer; from epigenetic silencing to functional characterization. Biochim Biophys Acta 1796:114–128. doi: 10.1016/j.bbcan.2009.03.004 PubMedGoogle Scholar
  12. 12.
    Gao T, Wang S, He B, Pan Y, Song G, Gu L, Chen L, Nie Z et al (2012) The association of RAS association domain family protein1A (RASSF1A) methylation states and bladder cancer risk: a systematic review and meta-analysis. PLoS One 7:e48300. doi: 10.1371/journal.pone.0048300 PubMedCentralCrossRefPubMedGoogle Scholar
  13. 13.
    Xu B, Di J, Wang Z, Han X, Li Z, Luo X, Zheng Q (2013) Quantitative analysis of RASSF1A promoter methylation in hepatocellular carcinoma and its prognostic implications. Biochem Biophys Res Commun 438:324–328. doi: 10.1016/j.bbrc.2013.07.070 CrossRefPubMedGoogle Scholar
  14. 14.
    Saelee P, Wongkham S, Chariyalertsak S, Petmitr S, Chuensumran U (2010) Rassf1a promoter hypermethylation as a prognostic marker for hepatocellular carcinoma. Asian Pac J Cancer Prev 11:1677–1681. http://www.ncbi.nlm.nih.gov/pubmed/21338215 Google Scholar
  15. 15.
    Lorente A, Mueller W, Urdangarin E, Lazcoz P, Lass U, von Deimling A, Castresana JS (2009) RASSF1A, BLU, NORE1A, PTEN and MGMT expression and promoter methylation in gliomas and glioma cell lines and evidence of deregulated expression of de novo DNMTS. Brain Pathol 19:279–292. doi: 10.1111/j.1750-3639.2008.00185.x CrossRefPubMedGoogle Scholar
  16. 16.
    Wang J, Wang B, Chen X, Bi J (2011) The prognostic value of RASSF1A promoter hypermethylation in non-small cell lung carcinoma: a systematic review and meta-analysis. Carcinogenesis 32:411–416. doi: 10.1093/carcin/bgq266 CrossRefPubMedGoogle Scholar
  17. 17.
    Feng Q, Stern JE, Hawes SE, Lu H, Jiang M, Kiviat NB (2010) DNA methylation changes in normal liver tissues and hepatocellular carcinoma with different viral infection. Exp Mol Pathol 88:287–292. doi: 10.1016/j.yexmp.2010.01.002 PubMedCentralCrossRefPubMedGoogle Scholar
  18. 18.
    Honda S, Haruta M, Sugawara W, Sasaki F, Ohira M, Matsunaga T, Yamaoka H, Horie H et al (2008) The methylation status of RASSF1A promoter predicts responsiveness to chemotherapy and eventual cure in hepatoblastoma patients. Int J Cancer 123:1117–1125. doi: 10.1002/ijc.23613 CrossRefPubMedGoogle Scholar
  19. 19.
    Qiu XQ, Chen G, Yu HP, Hu L (2009) Detection of RASSF1A promoter hypermethylation in plasma of patients with primary hepatocellular carcinoma and its clinical significance. World Chin J Digestol 17:90–93Google Scholar
  20. 20.
    Vivekanandan P, Torbenson M (2008) Epigenetic instability is rare in fibrolamellar carcinomas but common in viral-associated hepatocellular carcinomas. Mod Pathol 21:670–675. doi: 10.1038/modpathol.2008.32 CrossRefPubMedGoogle Scholar
  21. 21.
    Stang A (2010) Critical evaluation of the newcastle–ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25:603–605. doi: 10.1007/s10654-010-9491-z CrossRefPubMedGoogle Scholar
  22. 22.
    Zintzaras E, Ioannidis JP (2005) HEGESMA: genome search meta-analysis and heterogeneity testing. Bioinformatics 21:3672–3673. doi: 10.1093/bioinformatics/bti536 CrossRefPubMedGoogle Scholar
  23. 23.
    Peters JL, Sutton AJ, Jones DR, Abrams KR, Rushton L (2006) Comparison of two methods to detect publication bias in meta-analysis. JAMA 295:676–680. doi: 10.1001/jama.295.6.676 CrossRefPubMedGoogle Scholar
  24. 24.
    Chen WS, Guo SL (2011) Methylation status of RASSF1 gene promoter in primary hepatocellular carcinoma and its clinical applications. China J Mod Med 21:1864–1867Google Scholar
  25. 25.
    Chen TG, Li JG, Lin ZC (2013) Promoter methylation of RASSF1A gene in hepatocellular carcinoma and its clinical significance. Chin J Gen Surg 28:300–303. doi: 10.3760/cma.j.issn.1007-631X.2013.04.016 Google Scholar
  26. 26.
    Fei BJ, Huang ZH, Hua D, Hu Y, Chen ZH, Yu J (2011) Clinical significance of methylation of plasma Ras-association domain family 1A gene in the molecular diagnosis of hepatocellular carcinoma. Tumor 31:742–747Google Scholar
  27. 27.
    Zhang YY, Jiang Q, Chen SQ, Gu RM, Zhang XM, Zhu M, Ma GJ (2013) Effects of DNA methylation and micronucleus formation on pathogenesis of hepatocellular carcinoma by methylation-specific polymerase chain reaction and microscopy. Chin J Biomed End 19:11–15. doi: 10.3760/cma.j.issn.1674-1927.2013.01.003 Google Scholar
  28. 28.
    Zhao QZ, Qi ZF, Wei WL, Li KZ, Dou KF (2006) Diagnostic value of detection of aberrantly methylated RASSF1A in plasma of patients with hepatocellular carcinoma. J Fourth Mil Med Univ 27:1577–1579Google Scholar
  29. 29.
    He QF, Yan D, Wang LX (2010) Promoter hypermethylation of RASSF1A and p16 gene in plasma of patients with hepatocellular carcinoma. Chin J Public Health 26:819–821Google Scholar
  30. 30.
    Gong HY, Liu ZG, Zhang HY (2011) Detection of promoter hypermethylation of RASSF1A and CDH13 gene by nested methylation specific polymerase chain reaction in hepatocellular carcinoma patients. Life Sci Res 15:56–60Google Scholar
  31. 31.
    Zhang X, Li HM, Liu Z, Zhou G, Zhang Q, Zhang T, Zhang J, Zhang C (2013) Loss of heterozygosity and methylation of multiple tumor suppressor genes on chromosome 3 in hepatocellular carcinoma. J Gastroenterol 48:132–143. doi: 10.1007/s00535-012-0621-0 CrossRefPubMedGoogle Scholar
  32. 32.
    Zhang YJ, Wu HC, Shen J, Ahsan H, Tsai WY, Yang HI, Wang LY, Chen SY et al (2007) Predicting hepatocellular carcinoma by detection of aberrant promoter methylation in serum DNA. Clin Cancer Res 13:2378–2384. doi: 10.1158/1078-0432.ccr-06-1900 CrossRefPubMedGoogle Scholar
  33. 33.
    Yeo W, Wong N, Wong WL, Lai PB, Zhong S, Johnson PJ (2005) High frequency of promoter hypermethylation of RASSF1A in tumor and plasma of patients with hepatocellular carcinoma. Liver Int 25:266–272. doi: 10.1111/j.1478-3231.2005.01084.x CrossRefPubMedGoogle Scholar
  34. 34.
    Schagdarsurengin U, Wilkens L, Steinemann D, Flemming P, Kreipe HH, Pfeifer GP, Schlegelberger B, Dammann R (2003) Frequent epigenetic inactivation of the RASSF1A gene in hepatocellular carcinoma. Oncogene 22:1866–1871. doi: 10.1038/sj.onc.1206338 CrossRefPubMedGoogle Scholar
  35. 35.
    Mohamed NA, Swify EM, Amin NF, Soliman MM, Tag-Eldin LM, Elsherbiny NM (2012) Is serum level of methylated RASSF1A valuable in diagnosing hepatocellular carcinoma in patients with chronic viral hepatitis c? Arab J Gastroenterol 13:111–115. doi: 10.1016/j.ajg.2012.06.009 CrossRefPubMedGoogle Scholar
  36. 36.
    Lou C, Du Z, Yang B, Gao Y, Wang Y, Fang S (2009) Aberrant DNA methylation profile of hepatocellular carcinoma and surgically resected margin. Cancer Sci 100:996–1004. doi: 10.1111/j.1349-7006.2009.01138.x CrossRefPubMedGoogle Scholar
  37. 37.
    Feng Y, Xue WJ, Li P, Sha ZY, Huang H, Rui L, Li HX, Mao QS (2012) Rassf1a hypermethylation is associated with aflatoxin b1 and polycyclic aromatic hydrocarbon exposure in hepatocellular carcinoma. Hepatogastroenterology 59:1883–1888. doi: 10.5754/hge11731 PubMedGoogle Scholar
  38. 38.
    Chan KC, Lai PB, Mok TS, Chan HL, Ding C, Yeung SW, Lo YM (2008) Quantitative analysis of circulating methylated DNA as a biomarker for hepatocellular carcinoma. Clin Chem 54:1528–1536. doi: 10.1373/clinchem.2008.104653 CrossRefPubMedGoogle Scholar
  39. 39.
    Calvisi DF, Ladu S, Gorden A, Farina M, Conner EA, Lee JS, Factor VM, Thorgeirsson SS (2006) Ubiquitous activation of ras and jak/stat pathways in human hcc. Gastroenterology 130:1117–1128. doi: 10.1053/j.gastro.2006.01.006 CrossRefPubMedGoogle Scholar
  40. 40.
    Tischoff I, Markwarth A, Witzigmann H, Uhlmann D, Hauss J, Mirmohammadsadegh A, Wittekind C, Hengge UR et al (2005) Allele loss and epigenetic inactivation of 3p21.3 in malignant liver tumors. Int J Cancer 115:684–689. doi: 10.1002/ijc.20944 CrossRefPubMedGoogle Scholar
  41. 41.
    Richter AM, Schagdarsurengin U, Rastetter M, Steinmann K, Dammann RH (2010) Protein kinase A-mediated phosphorylation of the RASSF1A tumour suppressor at serine 203 and regulation of RASSF1A function. Eur J Cancer 46:2986–2995. doi: 10.1016/j.ejca.2010.06.128 CrossRefPubMedGoogle Scholar
  42. 42.
    Tian Y, Hou Y, Zhou X, Cheng H, Zhou R (2011) Tumor suppressor rassf1a promoter: P53 binding and methylation. PLoS One 6:e17017. doi: 10.1371/journal.pone.0017017 PubMedCentralCrossRefPubMedGoogle Scholar
  43. 43.
    Bayram S (2012) RASSF1A ALA133SER polymorphism is associated with increased susceptibility to hepatocellular carcinoma in a Turkish population. Gene 498:264–269. doi: 10.1016/j.gene.2012.02.040 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Yong-Shuang Li
    • 1
    Email author
  • Qiang Xie
    • 1
  • Da-Ye Yang
    • 1
  • Yuan Zheng
    • 1
  1. 1.Department of Emergency SurgeryThe Fourth Affiliated Hospital of China Medical UniversityHuanggu DistrictPeople’s Republic of China

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