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Survivin T9809C, an SNP Located in 3′-UTR, Displays a Correlation with the Risk and Clinicopathological Development of Hepatocellular Carcinoma

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Early detection of hepatocellular carcinoma (HCC) is seldom available because of the lack of reliable markers. Survivin is an anti-apoptotic protein that is implicated in the regulation of apoptosis and cell cycle, and it is undetectable in normal adult tissues but is overexpressed in various types of cancers. Survivin is thus commonly considered to be a marker of malignancy. The aim of this study was to explore the association between survivin gene polymorphisms and the risk and diagnostic progress of HCC.

Methods

A total of 135 patients with HCC and 496 healthy control subjects were recruited. Five single nucleotide polymorphisms (SNPs) of survivin genes were determined by real-time polymerase chain reaction (real-time PCR) and further analyzed statistically.

Results

We first found that the −241 C/T and −235 G/A genetic polymorphisms of survivin did not occur frequently enough or even lacked in Taiwanese population. The +9809 C/C polymorphism exhibited a significant (P < .05) low risk of 0.525-fold (95% confidence interval [95% CI] = 0.297–0.930) to have HCC compared with the wild-type homozygotes and a low ratio of 0.214-fold (95% CI = 0.051–0.890) for positive anti-HCV was shown in the individuals with survivin +9809 polymorphic CC allele compared with the TT/TC genotypic subgroup.

Conclusions

Survivin +9809 polymorphic genotype is associated with the risk of HCC, and the HCC patients with survivin +9809 CC homozygotes might have a low risk of developing infected HCV-dependent HCC. The results suggest that the survivin T9809C SNP might contribute to the prediction of susceptibility and pathological development to HCC.

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References

  1. Altieri DC. Survivin, versatile modulation of cell division and apoptosis in cancer. Oncogene 2003;22:8581–9.

    Article  PubMed  CAS  Google Scholar 

  2. Ambrosini G, Adida C, Sirugo G, Altieri DC. Induction of apoptosis and inhibition of cell proliferation by BIRC5 gene targeting. J Biol Chem. 1998;273:11177–82.

    Article  PubMed  CAS  Google Scholar 

  3. Yang L, Zhu H, Zhou B, Gu H, Yan H, Tang N, et al. The association between the survivin C-31G polymorphism and gastric cancer risk in a Chinese population. Dig Dis Sci. 2009;54:1021–8.

    Article  PubMed  CAS  Google Scholar 

  4. Kawamura K, Sato N, Fukuda J, Kodama H, Kumagai J, Tanikawa H, et al. Survivin acts as an antiapoptotic factor during the development of mouse preimplantation embryos. Dev. Biol. 2003;256:331–41.

    Article  PubMed  CAS  Google Scholar 

  5. Salvesen GS, Duckett CS. IAP proteins: blocking the road to death’s door. Nat Rev Mol Cell Biol. 2002;3:401–10.

    Article  PubMed  CAS  Google Scholar 

  6. Altieri DC. The molecular basis and potential role of survivin in cancer diagnosis and therapy. Trends Mol Med. 2001;7:542–7.

    Article  PubMed  CAS  Google Scholar 

  7. Duffy MJ, O’Donovan N, Brennan DJ, Gallagher WM, Ryan BM. Survivin: a promising tumor biomarker. Cancer Lett. 2007;249:49–60.

    Article  PubMed  CAS  Google Scholar 

  8. Shariat SF, Ashfaq R, Karakiewicz PI, Saeedi O, Sagalowsky AI, Lotan Y. Survivin expression is associated with bladder cancer presence, stage, progression, and mortality. Cancer. 2007;109:1106–13.

    Article  PubMed  CAS  Google Scholar 

  9. Shastry BS. SNP alleles in human disease and evolution. J Hum Genet. 2002;47:561–6.

    Article  PubMed  CAS  Google Scholar 

  10. Weng CJ, Hsieh YH, Tsai CM, Chu YH, Ueng KC, Liu YF, et al. Relationship of insulin-like growth factors system gene polymorphisms with the susceptibility and pathological development of hepatocellular carcinoma. Ann Surg Oncol. 2010;17:1808–15.

    Article  PubMed  Google Scholar 

  11. Farazi PA, DePinho RA. Hepatocellular carcinoma pathogenesis: from genes to environment. Nat Rev Cancer. 2006;6:674–87.

    Article  PubMed  CAS  Google Scholar 

  12. Firpi RJ, Nelson DR. Viral hepatitis: manifestations and management strategy. Hematol Am Soc Hematol Educ Program. 2006;375–80.

  13. Yano Y, Yamashita F, Kuwaki K, Fukumori K, Kato O, Yamamoto H, et al. Clinical features of hepatitis C virus-related hepatocellular carcinoma and their association with alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II. Liver Int. 2006;26:789–95.

    Article  PubMed  CAS  Google Scholar 

  14. Feitelson MA. Parallel epigenetic and genetic changes in the pathogenesis of hepatitis virus-associated hepatocellular carcinoma. Cancer Lett. 2006;239:10–20.

    Article  PubMed  CAS  Google Scholar 

  15. Weng CJ, Tsai CM, Chen YC, Hsieh YH, Lin CW, Liu YF, et al. Evaluation of the association of urokinase plasminogen activator system gene polymorphisms with susceptibility and pathological development of hepatocellular carcinoma. Ann Surg Oncol. 2010;17:3394–401.

    Article  PubMed  Google Scholar 

  16. Chen TY, Li YC, Liu YF, Tsai CM, Hsieh YH, Lin CW, et al. Role of MMP14 gene polymorphisms in susceptibility and pathological development to hepatocellular carcinoma. Ann Surg Oncol. 2011;18:2348–56.

    Article  PubMed  Google Scholar 

  17. Thorgeirsson SS, Grisham JW. Molecular pathogenesis of human hepatocellular carcinoma. Nat Genet. 2002;31:339–46.

    Article  PubMed  CAS  Google Scholar 

  18. Adida C, Crotty PL, McGrath J, Berrebi D, Diebold J, Altieri DC. Developmentally regulated expression of the novel cancer antiapoptosis gene survivin in human and mouse differentiation. Am J Pathol. 1998;152:43–9.

    PubMed  CAS  Google Scholar 

  19. Gianani R, Jarboe E, Orlicky D, Frost M, Bobak J, Lehner R, et al. Expression of survivin in normal, hyperplastic, and neoplastic colonic mucosa. Hum Pathol. 2001;32:119–25.

    Article  PubMed  CAS  Google Scholar 

  20. Falleni M, Pellegrini C, Marchetti A, Oprandi B, Buttitta F, Barassi F, et al. Survivin gene expression in early-stage nonsmall cell lung cancer. J Pathol. 2003;200:620–6.

    Article  PubMed  CAS  Google Scholar 

  21. Chen CJ, Yu MW, Liaw YF. Epidemiological characteristics and risk factors of hepatocellular carcinoma. J Gastroenterol Hepatol. 1997;12:S294–S308.

    Article  PubMed  CAS  Google Scholar 

  22. Chen TH, Chen CJ, Yen MF, Lu SN, Sun CA, Huang GT, et al. Ultrasound screening and risk factors for death from hepatocellular carcinoma in a high risk group in Taiwan. Int J Cancer. 2002;98:257–61.

    Article  PubMed  CAS  Google Scholar 

  23. Tsai MC, Kee KM, Chen YD, Lin LC, Tsai LS, Chen HH, et al. Excess mortality of hepatocellular carcinoma and morbidity of liver cirrhosis and hepatitis in HCV-endemic areas in an HBV-endemic country: geographic variations among 502 villages in southern Taiwan. J Gastroenterol Hepatol. 2007;22:92–8.

    Article  PubMed  Google Scholar 

  24. Akkiz H, Bayram S, Bekar A, Ozdil B, Akgöllü E, Sümbül AT, et al. G-308A TNF-alpha polymorphism is associated with an increased risk of hepatocellular carcinoma in the Turkish population: case-control study. Cancer Epidemiol. 2009;33:261–4.

    Article  PubMed  CAS  Google Scholar 

  25. Chang CC, Chen SC, Hsieh YH, Chen YC, Chen TY, Chu YH, et al. Stromal cell-derived factor-1 but not its receptor, CXCR4, gene variants increase susceptibility and pathological development of hepatocellular carcinoma. Clin Chem Lab Med. 2009;47:412–8.

    Article  PubMed  CAS  Google Scholar 

  26. Buendia MA. Genetics of hepatocellular carcinoma. Semin Cancer Biol. 2000;10:185–200.

    Article  PubMed  CAS  Google Scholar 

  27. Cheng ZJ, Hu LH, Huang SJ. Correlation of −31G/C polymorphisms of survivin promoter to tumorigenesis of gastric carcinoma. Ai Zheng. 2008;27:258–63.

    PubMed  CAS  Google Scholar 

  28. Jang JS, Kim KM, Kang KH, Choi JE, Lee WK, Kim CH, et al. Polymorphisms in the survivin gene and the risk of lung cancer. Lung Cancer. 2008;60:31–9.

    Article  PubMed  Google Scholar 

  29. Gazouli M, Tzanakis N, Rallis G, Theodoropoulos G, Papaconstantinou I, Kostakis A, et al. Survivin −31G/C promoter polymorphism and sporadic colorectal cancer. Int J Colorectal Dis. 2009;24:145–50.

    Article  PubMed  Google Scholar 

  30. Xu Y, Fang F, Ludewig G, Jones G, Jones D. A mutation found in the promoter region of the human survivin gene is correlated to overexpression of survivin in cancer cells. DNA Cell Biol. 2004;23:527–37.

    PubMed  CAS  Google Scholar 

  31. Han CH, Wei Q, Lu KK, Liu Z, Mills GB, Wang LE. Polymorphisms in the survivin promoter are associated with age of onset of ovarian cancer. Int J Clin Exp Med. 2009;2:289–99.

    PubMed  CAS  Google Scholar 

  32. Borbely AA, Murvai M, Szarka K, Konya J, Gergely L, Hernadi Z, Veress G. Survivin promoter polymorphism and cervical carcinogenesis. J Clin Pathol. 2007;60:303–6.

    Article  PubMed  CAS  Google Scholar 

  33. Yang X, Xiong G, Chen X, Xu X, Wang K, Fu Y, et al. Polymorphisms of survivin promoter are associated with risk of esophageal squamous cell carcinoma. J Cancer Res Clin Oncol. 2009;135:1341–9.

    Article  PubMed  CAS  Google Scholar 

  34. Boidot R, Vegran F, Jacob D, Chevrier S, Gangneux N, Taboureau J, et al. The expression of BIRC5 is correlated with loss of specific chromosomal regions in breast carcinomas. Gene Chromosomes Cancer. 2008;47:299–308.

    Article  CAS  Google Scholar 

  35. Boidot R, Végran F, Jacob D, Chevrier S, Cadouot M, Feron O, et al. The transcription factor GATA-1 is overexpressed in breast carcinomas and contributes to survivin upregulation via a promoter polymorphism. Oncogene. 2010;29:2577–84.

    Article  PubMed  CAS  Google Scholar 

  36. Majoros WH, Ohler U. Spatial preferences of microRNA targets in 3′ untranslated regions. BMC Genomics. 2007;8:152.

    Article  PubMed  Google Scholar 

  37. Vegran F, Boidot R, Oudin C, Riedinger JM, Lizard-Nacol S. Distinct expression of Survivin splice variants in breast carcinomas. Int J Oncol. 2005;27:1151–7.

    PubMed  CAS  Google Scholar 

  38. Antonacopoulou AG, Floratou K, Bravou V, Kottorou A, Dimitrakopoulos FI, Marousi S, et al. The survivin −31 snp in human colorectal cancer correlates with survivin splice variant expression and improved overall survival. Anal Cell Pathol (Amst). 2010;33:177–89.

    CAS  Google Scholar 

  39. Saitoh W, Sakamoto T, Hegab AE, Nomura A, Ishii Y, Morishima Y, et al. MMP14 gene polymorphisms in chronic obstructive pulmonary disease. Int J Mol Med. 2006;17:621–6.

    PubMed  CAS  Google Scholar 

  40. Schwarz KB. Oxidative stress during viral infection: a review. Free Radical Biol Med. 1996;21:641–9.

    Article  CAS  Google Scholar 

  41. Mansouri A, Fromenty B, Berson A, Robin MA, Grimbert S, Beaugrand M, et al. Multiple hepatic mitochondrial DNA deletions suggest premature oxidative aging in alcoholic patients. J Hepatol. 1997;27:96–102.

    Article  PubMed  CAS  Google Scholar 

  42. Merican I, Guan R, Amarapuka D, Alexander MJ, Chutaputti A, Chien RN, et al. Chronic hepatitis B virus infection in Asian countries. J Gastroenterol Hepatol 2000;15:1356–61.

    Article  PubMed  CAS  Google Scholar 

  43. Lavanchy D. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepatitis. 2004;11:97–107.

    Article  CAS  Google Scholar 

  44. Wang BE, Ma WM, Sulaiman A, Noer S, Sumoharjo S, Sumarsidi D, et al. Demographic, clinical, and virological characteristics of hepatocellular carcinoma in Asia: survey of 414 patients from four countries. J Med Virol. 2002;67:394–400.

    Article  PubMed  Google Scholar 

Download references

Acknowledgment

This study was partially supported by the National Science Council, NSC99-2313-B-165-001-MY3, Taiwan, Republic of China.

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Authors and Affiliations

  1. Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan

    Yih-Shou Hsieh PhD

  2. Department of Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan

    Yih-Shou Hsieh PhD

  3. Hualien Hospital, Department of Health, Executive Yuan, Hualien City, Hualien County, Taiwan

    Chiung-Man Tsai MS

  4. School of Medicine, Chung Shan Medical University, Taichung, Taiwan

    Chao-Bin Yeh MD, PhD

  5. Department of Emergency Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan

    Chao-Bin Yeh MD, PhD

  6. Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan

    Shun-Fa Yang PhD

  7. Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan

    Shun-Fa Yang PhD

  8. Institute of Biochemistry and Biotechnology, School of Medicine, Chung Shan Medical University, Taichung, Taiwan

    Yi-Hsien Hsieh PhD

  9. Graduate Institute of Applied Science of Living, Tainan University of Technology, Tainan, Taiwan

    Chia-Jui Weng PhD

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  1. Yih-Shou Hsieh PhD
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Correspondence to Chia-Jui Weng PhD.

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Hsieh, YS., Tsai, CM., Yeh, CB. et al. Survivin T9809C, an SNP Located in 3′-UTR, Displays a Correlation with the Risk and Clinicopathological Development of Hepatocellular Carcinoma. Ann Surg Oncol 19 (Suppl 3), 625–633 (2012). https://doi.org/10.1245/s10434-011-2123-3

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  • DOI: https://doi.org/10.1245/s10434-011-2123-3

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