Lingeng Lu1, Stephen G Gaffney2, Vincent L Cannataro2, Jeffrey Townsend2. 1. Department of Chronic Disease Epidemiology, Yale School of Public Health, School of Medicine, Center for Biomedical Data Science, Yale Cancer Center, Yale University, 60 College Street, New Haven, CT 06520-8034, USA. Electronic address: lingeng.lu@yale.edu. 2. Department of Biostatistics, Yale School of Public Health, Yale University, New Haven, CT, 06520, USA.
Abstract
OBJECTIVES: To investigate how T-cell activation interacts with NSUN2 to influence HNSCC patient survival. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
OBJECTIVES: To investigate how T-cell activation interacts with NSUN2 to influence HNSCC patient survival. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
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