Potential impact of micro-196a2 and Toll-like receptor 2 gene polymorphisms on oral cancer prognosis and susceptibility

Objective

Despite advances in diagnosis and treatment in recent years, oral squamous cell carcinoma (OSCC) is still associated with a high recurrence rate and poor survival. MiR-196a2 and TLR2 have been implicated in cancer progression and prognosis, but the significance of their genetic variants in OSCC remains unelucidated.

Design

This study investigated the miR-196a2 rs11614913 and TLR2 rs5743708 genetic variants in Caucasian HPV-negative OSCC patients (n = 95) and age- and sex-matched healthy controls (n = 108) using real-time PCR. An assessment was conducted on their association with clinicopathological features, overall survival (OS), recurrence-free survival (RFS) and OSCC risk.

Results

OSCC patients carrying the miR-196a2 rs11614913 TT genotype had a higher risk of tumor recurrence (P = 0.045) and shorter RFS (P = 0.041). The proportional hazards assumption was violated for tumor stage. Stage-stratified Kaplan-Meier analysis showed that miR-196a2 rs11614913 genotypes and combined CC+CT vs. TT variants significantly affected RFS in stage I/II OSCC patients (P = 0.012 and P = 0.003, respectively), but not in advanced stage III/IV patients (P = 0.545 and P = 0.287, respectively). Cox regression confirmed miR-196a2 rs11614913 as an independent predictor of RFS in early stage (HR=3.407, P = 0.015), but not in advance stage patients (HR=1.090, P = 0.711). No significant associations with OS were found. Additionally, the TLR2 rs5743708 variant allele A was significantly associated with a lower risk of OSCC (Adjusted OR=0.406, P = 0.013).

Conclusions

These findings suggest that miR-196a2 rs11614913 could play a stage-dependent role in RFS, influencing early-stage OSCC but losing prognostic significance in advanced disease. Additionally, TLR2 rs5743708 may contribute to the decreased OSCC risk.