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Tumor Biology

, Volume 35, Issue 2, pp 967–971 | Cite as

Aberrant TIG1 methylation associated with its decreased expression and clinicopathological significance in hepatocellular carcinoma

Research Article

Abstract

Recently, it has been reported that tazarotene-induced gene 1 (TIG1) methylation was frequently detected in a variety of human cancers. However, the relationship between the TIG1 methylation and the characteristics of hepatocellular carcinoma (HCC) remains unknown. The aim of present study was to observe the promoter methylation of TIG1 in HCC tissues and assess its prognostic significance for HCC. Real-time quantitative polymerase chain reaction and methylation-specific polymerase chain reaction were used, respectively, to examine the mRNA expression and methylation status of TIG1 in 91 pairs of HCC and adjacent noncancerous tissues. The mRNA expression level of TIG1 was significantly lower in HCC tissues than in adjacent noncancerous tissues. The rate of TIG1 promoter methylation was significantly higher in HCC tissues than in adjacent noncancerous tissues (P < 0.001). A strong correlation between downregulation and promoter methylation was found in these tumors (P < 0.001). More importantly, TIG1 methylation status was related to tumor size (P = 0.015), histological differentiation (P = 0.004), and tumor stage (P < 0.001). Kaplan–Meier survival analysis showed that TIG1 promoter hypermethylation was associated with a worse outcome in patients with HCC. Further, Cox multivariate analysis indicated that TIG1 methylation status was an independent prognostic factor for the overall survival rate of HCC patients. In conclusion, our data suggested that epigenetic silencing of TIG1 gene expression by promoter hypermethylation may play an important role in HCC.

Keywords

TIG1 Methylation MSP Prognosis 

Notes

Conflicts of interest

None

References

  1. 1.
    Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90. doi: 10.3322/caac.20107.PubMedCrossRefGoogle Scholar
  2. 2.
    Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology. 2005;42:1208–36.PubMedCrossRefGoogle Scholar
  3. 3.
    Llovet JM. UHCCted treatment approach to hepatocellular carcinoma. J Gastroenterol. 2005;40:225–35.PubMedCrossRefGoogle Scholar
  4. 4.
    Bruix J, Boix L, Sala M, Llovet JM. Focus on hepatocellular carcinoma. Cancer Cell. 2004;5:215–9.PubMedCrossRefGoogle Scholar
  5. 5.
    Jin W, Lee JJ, Kim MS, Son BH, Cho YK, Kim HP. DNA methylation-dependent regulation of TrkA, TrkB, and TrkC genes in human hepatocellular carcinoma. Biochem Biophys Res Commun. 2011;406:89–95. doi: 10.1016/j.bbrc.2011.01.116.PubMedCrossRefGoogle Scholar
  6. 6.
    Goeppert B, Schmezer P, Dutruel C, Oakes C, Renner M, Breinig M, et al. Down-regulation of tumor suppressor A kinase anchor protein 12 in human hepatocarcinogenesis by epigenetic mechanisms. Hepatology. 2010;52:2023–33. doi: 10.1002/hep.23939.PubMedCrossRefGoogle Scholar
  7. 7.
    Sun JZ, Yang XX, Li XH, Xu WW, Wang Y, Zhu W, et al. Aberrant CpG island hypermethylation and down-regulation of Oct-6 mRNA expression in human hepatocellular carcinoma. Dig Dis Sci. 2011;56:3072–7. doi: 10.1007/s10620-011-1686-y.PubMedCrossRefGoogle Scholar
  8. 8.
    Liu H, Dong H, Robertson K, Liu C. DNA methylation suppresses expression of the urea cycle enzyme carbamoyl phosphate synthetase 1 (CPS1) in human hepatocellular carcinoma. Am J Pathol. 2011;178:652–61. doi: 10.1016/j.ajpath.2010.10.023.PubMedCrossRefGoogle Scholar
  9. 9.
    Nagpal S, Patel S, Asano AT, Johnson AT, Duvic M, Chandraratna RA. Tazarotene-induced gene 1 (TIG1), a novel retinoic acid receptor-responsive gene in skin. J Invest Dermatol. 1996;106:269–74.PubMedCrossRefGoogle Scholar
  10. 10.
    Zhang J, Liu L, Pfeifer GP. Methylation of the retinoid response gene TIG1 in prostate cancer correlates with methylation of the retinoic acid receptor beta gene. Oncogene. 2004;23:2241–9. doi: 10.1038/sj.onc.1207328.PubMedCrossRefGoogle Scholar
  11. 11.
    Jing C, El-Ghany MA, Beesley C, Foster CS, Rudland PS, Smith P, et al. Tazarotene-induced gene 1 (TIG1) expression in prostate carcinomas and its relationship to tumorigenicity. J Natl Cancer Inst. 2002;94:482–90. doi: 10.1093/jnci/94.7.482.PubMedCrossRefGoogle Scholar
  12. 12.
    Lotan R. Is TIG1 a new tumor suppressor in prostate cancer? J Natl Cancer Inst. 2002;94:469–70. doi: 10.1093/jnci/94.7.469.PubMedCrossRefGoogle Scholar
  13. 13.
    Kwong J, Lo KW, Chow LS, Chan FL, To KF, Huang DP. Silencing of the retinoid response gene TIG1 by promoter hypermethylation in nasopharyngeal carcinoma. Int J Cancer. 2005;113:386–92. doi: 10.1002/ijc.20593.PubMedCrossRefGoogle Scholar
  14. 14.
    Son MS, Kang MJ, Park HC, Chi SG, Kim YH. Expression and mutation analysis of TIG1 (tazarotene-induced gene 1) in human gastric cancer. Oncol Res. 2009;17:571–80.PubMedCrossRefGoogle Scholar
  15. 15.
    Peng H, Long F, Wu Z, Chu Y, Li J, Kuai R, et al. Downregulation of TIG1 gene by promoter methylation during primary colorectal cancer progression. Biomed Res Int. 2013;2013:181384. doi: 10.1155/2013/181384.PubMedCentralPubMedGoogle Scholar
  16. 16.
    Shin SH, Park SY, Kang GH. Down-regulation of dual-specificity phosphatase 5 in gastric cancer by promoter CpG island hypermethylation and its potential role in carcinogenesis. Am J Pathol. 2013;182:1275–85. doi: 10.1016/j.ajpath.2013.01.004.PubMedCrossRefGoogle Scholar
  17. 17.
    Yoo TH, Ryu BK, Lee MG, Chi SG. CD81 is a candidate tumor suppressor gene in human gastric cancer. Cell Oncol (Dordr). 2013;36:141–53. doi: 10.1007/s13402-012-0119-z.PubMedCrossRefGoogle Scholar
  18. 18.
    Zhong X, Zhu Y, Mao J, Zhang J, Zheng S. Frequent epigenetic silencing of PCDH10 by methylation in human colorectal cancer. J Cancer Res Clin Oncol. 2013;139:485–90. doi: 10.1007/s00432-012-1353-5.PubMedCrossRefGoogle Scholar
  19. 19.
    Jin Z, Mori Y, Yang J, Sato F, Ito T, Cheng Y, et al. Hypermethylation of the nel-like 1 gene is a common and early event and is associated with poor prognosis in early-stage esophageal adenocarcinoma. Oncogene. 2007;26:6332–40. doi: 10.1038/sj.onc.1210461.PubMedCrossRefGoogle Scholar
  20. 20.
    Sun D, Zhang Z. Van do N, Huang G, Ernberg I, Hu L. Aberrant methylation of CDH13 gene in nasopharyngeal carcinoma could serve as a potential diagnostic biomarker. Oral Oncol. 2007;43:82–7.PubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  1. 1.Department of General SurgeryCixi People’s HospitalCixiChina
  2. 2.Department of General SurgeryXinhua Hospital Affiliated with Shanghai Jiaotong University School of MedicineShanghaiChina
  3. 3.Hangzhou Normal UniversityHangzhouChina

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