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Identification and validation of autophagy-related prognostic signature for head and neck squamous cell carcinoma
Authors:Jiayu Fang  Zhiqiang Yang  Jing Xie  Ziang Li  Chang Hu  Minlan Yang  Xuhong Zhou
Affiliation:aDepartment of Otorhinolaryngology-Head and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430000, China;bDepartment of Spine Surgery and Musculoskeletal Tumor, Zhongnan Hospital of Wuhan University, Wuhan, China;cDepartment of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China;dDepartment of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China
Abstract:BackgroundMany studies have demonstrated that autophagy plays a significant role in regulating tumor growth and progression. However, the effect of autophagy-related genes (ARGs) on the prognosis have rarely been analyzed in head and neck squamous cell carcinoma (HNSCC).MethodsWe obtained differentially expressed ARGs from HNSCC mRNA data in The Cancer Genome Atlas (TCGA) database. And then we performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to explore the autophagy-related biological functions. The overall survival (OS)-related and disease specific survival (DSS)-related ARGs were identified by univariate Cox regression analyses. With these genes, we established OS-related and DSS-related risk signature by LASSO regression method, respectively. We validated the reliability of the risk signature with receiver operating characteristic (ROC) analysis, Kaplan-Meier survival curves, clinical correlation analysis, and nomogram. Then we analyzed relationships between risk signature and immune cell infiltration.ResultsWe established the prognostic signatures based on 14 ARGs for OS and 12 ARGs for DSS. The ROC curves, survival analysis, and nomogram validated the predictive accuracy of the models. Clinic correlation analysis showed that the risk group was closely related to Stage, pathological T stage, pathological N stage and human papilloma virus (HPV) subtype. Cox regression demonstrated that the risk score was an independent predictor for the prognosis of HNSCC patients. Furthermore, patients in low-risk score group exhibited higher immunescore and distinct immune cell infiltration than high-risk score group. And we further analysis revealed that the copy number alterations (CNAs) of ARGs-based signature affected the abundance of tumor-infiltrating immune cells.ConclusionIn this study, we identified novel autophagy-related signature for the prediction of OS and DSS in patients with HNSCC. Meanwhile, our study provides a novel sight to understand the role of autophagy and elucidate the important role of autophagy in tumor immune microenvironment (TIME) of HNSCC.
Keywords:TCGA   Autophagy-related genes   Overall survival   Disease-specific survival   Prognostic risk signature   TIME
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