Genetic variations in monocarboxylate transporter genes as predictors of clinical outcomes in non-small cell lung cancer
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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 = 0.039). 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.
KeywordsNon-small cell lung cancer Single nucleotide polymorphisms Monocarboxylate transporters Prognosis
Conflicts of interest
This work was supported by the Program for New Century Excellent Talents in University, National Basic Research Program (2015CB553703).
- 4.Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA: Cancer J Clin. 2005;55(2):74–108.Google Scholar
- 14.Pertega-Gomes N, Vizcaino JR, Miranda-Goncalves V, Pinheiro C, Silva J, Pereira H, et al. Monocarboxylate transporter 4 (MCT4) and CD147 overexpression is associated with poor prognosis in prostate cancer. BMC Cancer. 2011;11:312. doi: 10.1186/1471-2407-11-312.CrossRefPubMedPubMedCentralGoogle Scholar
- 27.Gerlinger M, Santos CR, Spencer-Dene B, Martinez P, Endesfelder D, Burrell RA, et al. Genome-wide RNA interference analysis of renal carcinoma survival regulators identifies MCT4 as a Warburg effect metabolic target. J Pathol. 2012;227(2):146–56. doi: 10.1002/path.4006.CrossRefPubMedPubMedCentralGoogle Scholar
- 32.Cupeiro R, Gonzalez-Lamuno D, Amigo T, Peinado AB, Ruiz JR, Ortega FB, et al. Influence of the MCT1-T1470A polymorphism (rs1049434) on blood lactate accumulation during different circuit weight trainings in men and women. J Sci Med Sport / Sport Med Aust. 2012;15(6):541–7. doi: 10.1016/j.jsams.2012.03.009.CrossRefGoogle Scholar