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

Author:

Wang An12,Xiao Na13,Wang Hong1,Yao Qin1,Li Jin12,Wu Yaping12,Ge Han12,Diao Pengfei123ORCID

Affiliation:

1. Department of Oral and Maxillofacial Surgery The Affiliated Stomatological Hospital of Nanjing Medical University Jiangsu China

2. Jiangsu Key Laboratory of Oral Disease Nanjing Medical University Jiangsu China

3. Jiangsu Province Engineering Research Center of Stomatological Translational Medicine Nanjing Medical University Jiangsu China

Abstract

AbstractBackgroundCellular 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.MethodsOSCC‐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.ResultsThe 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.ConclusionsOur results established SRG‐derived signature/nomogram as powerful predictors for prognosis and chemotherapeutic response for OSCC.

Publisher

Wiley

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