Javid Jamsheed, Mir Rashid, Julka P K, Ray P C, Saxena Alpana
Cancer Genetics Lab, Department of Biochemistry, Maulana Azad Medical College and Associated hospitals, New Delhi, India.
Tumour Biol. 2015 Jul;36(7):5543-50. doi: 10.1007/s13277-015-3224-6. Epub 2015 Feb 14.
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.
生存素在胎儿组织中高表达，在终末分化细胞中完全缺失，但在大多数人类肿瘤中都观察到了它的重新表达。目前，我们旨在分析生存素基因（-31G>C，rs 9904341）启动子多态性对生存素基因表达谱的可能影响，以及生存素重新表达在非小细胞肺癌发生发展中的作用。对100例非小细胞肺癌患者和100例无癌健康对照进行了病例对照研究。采用聚合酶链反应-限制性片段长度多态性（RFLP）技术分析生存素基因启动子多态性，并用定量实时聚合酶链反应法评估生存素表达谱。与生存素GG基因型相比，发现纯合CC基因型的比值比为3.2（95%可信区间4.8-25.9，p=0.004），在非小细胞肺癌患者中生存素基因表达增加了15倍。随着疾病严重程度的增加，观察到生存素表达有显著的增加趋势。与生存素（-31GG）基因型携带者相比，生存素（-31CC）基因型患者的总生存期明显缩短。此外，生存素基因表达增加倍数较高的患者也反映出疾病进展和总生存期显著较差。总之，本研究表明生存素（-31G>C）多态性可能增加印度人群患非小细胞肺癌的风险。生存素（-31CC）基因型与生存素基因表达显著增加相关，最终可能导致非小细胞肺癌患者临床预后不良，提示其在非小细胞肺癌发生发展中可能具有重要意义。
