Pre-miRNA variants as predictors of clinical outcome in patients with squamous cell carcinomas of the nonoropharynx.

Abstract

Functional polymorphisms of miRNAs may affect the function and target expression of miRNAs, which can, in turn, affect the biological activity, etiology, and prognosis of cancer. We hypothesized that four common polymorphisms in pre-miRNAs (hsa-mir-146a rs2910164 G > C, hsa-mir-196a2 rs11614913 C > T, hsa-mir-149 rs2292832 G > T, and hsa-mir-499 rs3746444 A > G) are associated with survival in SCCNOP. We used univariate and multivariable Cox models to evaluate the associations between the four polymorphisms and survival. We found that hsa-mir-149 rs2292832 and hsa-mir-499 rs3746444 had statistically significant associations with survival, but hsa-mir-146a rs2910164 and hsa-mir-196a2 rs11614913 did not. Patients having the hsa-mir-149 CC and hsa-mir-499 TT wild-type genotypes had significantly better overall, disease-specific, and disease-free survival compared with those who had the corresponding variant CT/TT and CT/CC genotypes, respectively. Furthermore, these genotypes were significantly associated with reduced risk of overall death, death owing to disease, and recurrence after adjustment for important prognostic confounders, indicating that these pre-miRNA polymorphisms may be prognostic biomarkers for SCCNOP. Moreover, the stratified analyses based on smoking status and treatment indicated that the effects of hsa-mir-149 and hsa-mir-499 polymorphisms on survival were more pronounced in ever smokers and patients treated with chemoradiation. Our findings support that the hsa-mir-149 rs2292832 and hsa-mir-499 rs3746444 polymorphisms play a significant role in the prognosis of SCCNOP, especially in smokers and patients treated with chemoradiation. Prospective studies with larger sample sizes are needed to confirm these findings.