Role of survivin re-expression in the development and progression of non-small cell lung cancer

Tumour Biol. 2015 Jul;36(7):5543-50. doi: 10.1007/s13277-015-3224-6. Epub 2015 Feb 14.

Abstract

Survivin is highly expressed in fetal tissue and is completely absent in terminally differentiated cells, but its re-expression has been observed in most human tumors. Presently, we aimed to analyze the possible impact of the survivin gene (-31G > C, rs 9904341) promoter polymorphism on the expression profile of survivin gene and ultimately the role of survivin re-expression in the development and progression of non-small cell lung cancer. A case-control study of 100 non-small cell lung cancer patients and 100 cancer-free healthy controls was conducted. Survivin gene promoter polymorphism was analyzed by PCR-restriction fragment length polymorphisms (RFLP) technique, and the survivin expression profile was evaluated using quantitative real-time PCR assay. Compared to the survivin GG genotype, odd ratio of 3.2 (95 % CI 4.8-25.9, p = 0.004) was found to be associated to homozygous CC genotype with 15-fold increase of survivin gene expression in non-small cell lung cancer patients. Significant trend of increase in survivin expression was observed with the increase in severity of the disease. Patients with survivin (-31CC) genotype had significantly shorter overall survival compared to survivin (-31GG) genotype carriers. In addition, advanced disease status and significant poor overall survival were also reflected by patients with higher-fold increase in survivin gene expression. In conclusion, present study demonstrated that survivin (-31G > C) polymorphism may contribute to the risk of developing non-small cell lung cancer in Indian population. Survivin (-31CC) genotype was associated with significantly increased survivin gene expression and ultimately may contribute in the poor clinical outcome of non-small cell lung cancer patients, suggesting its possible significance in the development and progression of non-small cell lung cancer.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Asian People
  • Carcinoma, Non-Small-Cell Lung / epidemiology
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Inhibitor of Apoptosis Proteins / biosynthesis
  • Inhibitor of Apoptosis Proteins / genetics*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Polymorphism, Single Nucleotide
  • Prognosis*
  • Promoter Regions, Genetic
  • Survivin

Substances

  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • Survivin