title: Genetic variations in monocarboxylate transporter genes as predictors of clinical outcomes in non-small cell lung cancer.
abstract: Non-small cell lung cancer (NSCLC) is characterized by poor prognosis and only a few molecular markers may be potentially used to predict clinical outcomes. Previous studies have demonstrated that monocarboxylate transporters (MCTs) play important roles in the development and progression of many cancers. The purpose of this study was to assess the effects of single nucleotide polymorphisms (SNPs) of MCT genes on prognosis of NSCLC patients in Chinese Han population. Nine functional SNPs in MCT1, MCT2, and MCT4 genes were selected and genotyped using Sequenom iPLEX genotyping system in 500 Chinese NSCLC patients receiving surgery. Multivariate Cox proportional hazards model and Kaplan-Meier curve were used for the prognostic analysis. TT genotype of SNP rs1049434 (MCT1) was significantly associated with better overall survival (OS) (HR = 0.56, P = 0.026) and recurrence-free survival (RFS) (HR = 0.57, P = 0.016) of NSCLC patients. TT genotype of another SNP rs995343 (MCT2) exhibited an association with worse RFS of NSCLC patients (HR = 1.46, P =  .039). Unfavorable genotypes of SNP rs1049434 and rs995343 showed a significant cumulative effect on OS and RFS of NSCLC patients. Moreover, we found that patients carrying AA+AT genotypes of rs1049434 showed significant OS and RFS benefits from adjuvant chemotherapy, but those with TT genotype did not. Our findings suggest that SNPs in MCT1 and MCT2 genes may affect clinical outcomes and can be used to predict the response to adjuvant chemotherapy in NSCLC patients who received surgical treatment once validated in future study.
authors.affiliation: State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, 169 Changle West Road, Xi'an, 710032, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Guo
authors.forename: Cheng
authors.initials: C
authors.lastname: Chen
authors.forename: Boya
authors.initials: B
authors.lastname: Liu
authors.forename: Yousheng
authors.initials: Y
authors.lastname: Wu
authors.forename: Yibing
authors.initials: Y
authors.lastname: Chen
authors.forename: Xingchun
authors.initials: X
authors.lastname: Zhou
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Huang
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Li
authors.forename: Hushan
authors.initials: H
authors.lastname: Yang
authors.forename: Zhinan
authors.initials: Z
authors.lastname: Chen
authors.forename: Jinliang
authors.initials: J
authors.lastname: Xing
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D027501:Monocarboxylic Acid Transporters / Q000235:genetics*; D009124:Muscle Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011379:Prognosis; D027981:Symporters / Q000235:genetics*; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D014408:Biomarkers, Tumor; D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C406962:SLC16A4 protein, human; C490427:SLC16A7 protein, human