title: MicroRNA-related polymorphisms in apoptosis pathway genes are predictive of clinical outcome in patients with limited disease small cell lung cancer.
abstract: We examined the impact of single nucleotide polymorphisms (SNPs) at miRNA binding sites in the 3'-UTRs of genes in the apoptosis pathway on the prognosis of patients with limited disease-small cell lung cancer (LD-SCLC). Twelve tagSNPs in seven genes were genotyped using blood samples from 146 LD-SCLC patients treated with chemoradiotherapy. Cox proportional hazard regression models and recursive partitioning analysis were performed to identify SNPs significantly associated with overall survival. Three SNPs, CASP8: rs1045494 (C > T), PIK3R1: rs3756668 (A > G) and CASP7: rs4353229 (T > C), were associated with longer overall survival in LD-SCLC patients after chemoradiotherapy. The adjusted hazard ratios (95% confidence intervals) were 0.480 (0.258-0.894), 0.405 (0.173-0.947) and 0.446 (0.247-0.802), respectively, and remained significant after multiple comparison correction. Moreover, subset analysis showed these SNPs were still predictive of overall survival in stage III patients. Recursive partitioning analysis enabled patients to be classified into three risk subgroups based on unfavorable genotype combinations of the rs1045494 and rs4353229 SNPs. These findings suggest miRNA-related polymorphisms in the apoptosis pathway may be useful biomarkers for selection of LD-SCLC patients likely to benefit from chemoradiotherapy.
authors.affiliation: Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Bi
authors.affiliation: Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Wen-Jue
authors.initials: WJ
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Wu
authors.affiliation: Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Li-Pin
authors.initials: LP
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Men
authors.affiliation: Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Jing-Bo
authors.initials: JB
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liang
authors.affiliation: Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Zhou-Guang
authors.initials: ZG
authors.lastname: Hui
authors.affiliation: Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Zong-Mei
authors.initials: ZM
authors.lastname: Zhou
authors.affiliation: Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Lu-Hua
authors.initials: LH
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics*; D053179:Caspase 7 / Q000235:genetics; D053181:Caspase 8 / Q000235:genetics; D058543:Class Ia Phosphatidylinositol 3-Kinase; D005260:Female; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D055752:Small Cell Lung Carcinoma / Q000235:genetics* / Q000401:mortality
chemical_list: D020413:3' Untranslated Regions; D053179:Caspase 7; D053181:Caspase 8; D058543:Class Ia Phosphatidylinositol 3-Kinase; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; C588001:PIK3R1 protein, human; C505520:CASP7 protein, human; C505530:CASP8 protein, human
keywords: apoptosis pathway; limited disease; microRNA; single nucleotide polymorphisms; small cell lung cancer