Transfer RNA methyltransferase gene NSUN2 mRNA expression modifies the effect of T cell activation score on patient survival in head and neck squamous carcinoma.

Abstract

To investigate how T-cell activation interacts with NSUN2 to influence HNSCC patient survival. The relationships between T-cell activation status (Activation, Intermediate, and Exhaustion), NSUN2 expression, and patient survival were evaluated using Kaplan-Meier survival curves and multivariate Cox regression models in a public dataset with 520 HNSCC patients. HPV status was determined based on a VirusScan analysis of RNA-seq data. Among the patients with high NSUN2 expression, the Activation group exhibited longer survival than the Exhaustion group (trend P=0.056). Adjusted hazards ratios (HRs) were 0.77 (95% CI: 0.49-1.19) for the Intermediate vs Exhaustion, and 0.61 (0.36-1.03) for Activation vs. Exhaustion. In contrast, there is a positive association between T-cell activation score and mortality in the patients with low NSUN2 expression (trend P=0.016). The adjusted HRs were 1.97 (1.12-3.47) for the Intermediate vs Exhaustion, and 2.06 (1.16-3.68) for the Activation vs Exhaustion. In multivariate cox models with or without HPV status, the interaction between T-cell activation status and NSUN2 expression was statistically significant (P=0.004 for with HPV status, and P=0.002 for without, respectively). When not controlling for NSUN2 expression, there was no significant association between T-cell activation score and patient mortality (P=0.84). An interaction between NSUN2 expression and T-cell activation status affects patient survival in HNSCC regardless of HPV status, suggesting that NSUN2 is a potential precision marker for immune-checkpoint blockade, and a potential therapeutic target.