期刊名称：Computational and Structural Biotechnology Journal
印刷版ISSN：2001-0370
出版年度：2019
卷号：17
页码：1020-1030
DOI：10.1016/j.csbj.2019.07.009
出版社：Computational and Structural Biotechnology Journal
摘要：Although immunotherapy has emerged as an effective therapeutic strategy for various cancers including head and neck squamous cell carcinomas (HNSCCs), only a subset of patients can benefit from such therapy. Hence, it is pressing to discover predictive biomarkers for cancer immunotherapy response. TP53 and HRAS mutations frequently occur in HNSCC and correlate with a worse prognosis in HNSCC. We extensively characterized the associations of TP53 mutations and HRAS mutations with HNSCC immunity based on multiple cancer genomics datasets. We compared the enrichment levels of 20 immune signatures between TP53 -mutated and TP53 -wildtype HNSCCs, and between HRAS -mutated and HRAS -wildtype HNSCCs, and found that TP53 mutations were associated with depressed immune signatures while HRAS mutations were associated with enhanced immune signatures in HNSCC. Moreover, we found multiple p53- and RAS-mediated pathways showing significant correlations with HNSCC immunity. Furthermore, we demonstrated that the association between TP53 mutation and tumor immunity was independent of the human papillomavirus (HPV) infection and smoking status in HNSCC. These data suggest that p53 and RAS may play important roles in regulating HNSCC immunity and that the TP53 and HRAS mutation status could be useful biomarkers for stratifying HNSCC patients responsive to immunotherapy.
关键词：TP53 mutations ; HRAS mutations ; Head and neck squamous cell carcinomas ; Cancer genomics ; Tumor immunity ; APC Antigen-Presenting Cell ; BH Benjami and Hochberg ; DFS Disease Free Survival ; dMMR Deficient Mismatch-Repair ; EMT Epithelial-Mesenchymal Transition ; FDR False Discovery Rate ; GSEA Gene-Set Enrichment Analysis ; HLA Human Leukocyte Antigen ; HNSCC Head and Neck Squamous Cell Carcinomas ; HPV Human Papilloma Virus ; MHC Major Histocompatibility Complex ; NK Natural Killer ; OR Odds Ratio ; OS Overall Survival ; pDCs Plasmacytoid Dendritic Cells ; ssGSEA single-sample Gene-Set Enrichment Analysis ; TILs Tumor-Infiltrating Lymphocytes ; TIM Tumor Immune Microenvironment ; TMB Tumor Mutation Burden
