Development of a novel senescence-related gene signature to predict clinical outcomes, immune landscape, and chemotherapeutic sensitivity in oral squamous cell carcinoma.

BACKGROUND:Cellular senescence significantly associates with tumor initiation, progression, and therapeutic response across multiple cancers. Here, we sought to develop a novel senescence-related genes (SRGs)-derived signature for oral squamous cell carcinoma (OSCC) prognostication and therapeutic response prediction. METHODS:OSCC-specific SRG prognostic signature was established with univariate Cox regression, Kaplan-Meier survival, and LASSO-penalized multivariate Cox regression analyses. A SRG nomogram integrating this signature and selected clinicopathological parameters were constructed by multivariate Cox regression. SiRNA-mediated gene knockdown was exploited to validate its function in vitro. The utilities of SRG signature in predicting immune status and chemotherapeutic sensitivities were analyzed. RESULTS:The prognostic performance of SRG signature/nomogram was satisfactory in multiple independent cohorts. CDK1 knockdown induced senescence phenotype in vitro. Moreover, SRG signature scores negatively correlated with tumor-infiltrating immune cells and associated with multiple chemotherapeutic drug sensitivities. CONCLUSIONS:Our results established SRG-derived signature/nomogram as powerful predictors for prognosis and chemotherapeutic response for OSCC.