title: A microRNA-135a/b binding polymorphism in CD133 confers decreased risk and favorable prognosis of lung cancer in Chinese by reducing CD133 expression.
abstract: 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 rs2240688A>C 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, log-rank 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 hsa-miR-135a/b and decreased the CD133 expression. Our data suggest that the functional polymorphism rs2240688A>C 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.
authors.affiliation: The Institute for Chemical Carcinogenesis, The State Key Lab of Respiratory Disease, Guangzhou Medical University, 195 Dongfengxi Road, Guangzhou 510182, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Cheng
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.forename: Rongrong
authors.initials: R
authors.lastname: Yang
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Yang
authors.forename: Jieqiong
authors.initials: J
authors.lastname: Deng
authors.forename: Bolan
authors.initials: B
authors.lastname: Yu
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Huang
authors.forename: Shuxu
authors.initials: S
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Fuman
authors.initials: F
authors.lastname: Qiu
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Zhou
authors.forename: Jiachun
authors.initials: J
authors.lastname: Lu
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002681:China; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D010455:Peptides / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012306:Risk; D016019:Survival Analysis
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C544965:MIRN135 microRNA, human; D035683:MicroRNAs; C000606023:PROM1 protein, human; D010455:Peptides