A microrna-135a/b binding polymorphism in cd133 confers decreased risk and favorable prognosis of lung cancer in chinese by reducing cd133 expression

摘要

CD133 is a pivotal marker of cancer stem cells (CSCs), which is involved in tumorigenesis and cancer progression. Recent studies have identified CD133 to be a prognostic factor for cancer rested with its expression and genetic variants. Here, we hypothesized that the single nuclear polymorphisms (SNPs) in CD133 may be associated with lung cancer risk and prognosis. Based on three independent case-control analyses with a total of 2332 lung cancer cases and 2457 controls, the gene-based association analysis with 13 polymorphisms of CD133 suggested that CD133 is a susceptible gene for lung cancer (P = 0.043) and that the SNP rs2240688AC in the 3'-untranslated region of CD133 is the most significant associated SNP with the risk of lung cancer (P = 0.020); further analysis showed that the rs2240688C variant genotypes (CA+CC) harbored a decreased risk of lung cancer (odds ratio = 0.80; 95% confidence interval (CI) = 0.72-0.90) and conferred a favorable survival for lung cancer patients (median survival time: 15 months) compared with AA genotype (median survival time: 11 months, logrank test: P = 3.31 × 10-6; Cox model: hazards ratio = 0.81, 95% CI = 0.70-0.94). Functional assays revealed that the rs2240688A to rs2240688C transition gained a new binding of the microRNA hsamiR- 135a/b and decreased the CD133 expression. Our data suggest that the functional polymorphism rs2240688AC in CD133 is associated with lung cancer risk and survival. This SNP may be a functional biomarker to predict risk and prognosis of lung cancer.