Constructing a T-Cell Receptor-Related Gene Signature for Prognostic Stratification and Therapeutic Guidance in Head and Neck Squamous Cell Carcinoma

Abstract

Backgroud: The stratification of head and neck squamous cell carcinoma (HNSCC) patients based on prognostic differences is critical for therapeutic guidance. This study was designed to construct a predictive signature derived from T-cell receptor-related genes (TCRRGs) to forecast the clinical outcomes in HNSCC. Methods: We sourced gene expression profiles from The Cancer Genome Atlas (TCGA) HNSCC dataset, GSE41613, and GSE65858 datasets. Utilizing consensus clustering analysis, we identified two distinct HNSCC clusters according to TCRRG expression. A TCRRG-based signature was subsequently developed and validated across diverse independent HNSCC cohorts. Moreover, we established a nomogram model based on TCRRGs. We further explored differences in immune landscapes between high- and low-risk groups. Results: The TCGA HNSCC dataset was stratified into two clusters, displaying marked variations in both overall survival (OS) and immune cell infiltration. Furthermore, we developed a robust prognostic signature based on TCRRG utilizing the TCGA HNSCC train cohort, and its prognostic efficacy was validated in the TCGA HNSCC test cohort, GSE41613, and GSE65858. Importantly, the high-risk group was characterized by a suppressive immune microenvironment, in contrast to the low-risk group. Our study successfully developed a robust TCRRG-based signature that accurately predicts clinical outcomes in HNSCC, offering valuable strategies for improved treatments.