Abstract
Background and PurposeHead and neck squamous carcinoma (HNSCC), characterized by immunosuppression, is a group of highly heterogeneous cancers. Although immunotherapy exerts a promising influence on HNSCC, the response rate remains low and varies in assorted primary sites. Immunological mechanisms underlying HNSCC pathogenesis and treatment response are not fully understood. This study aimed to develop a differentially expressed genes (DEGs)–based risk model to predict immunotherapy efficacy and stratify prognosis of HNSCC patients.Materials and MethodsThe expression profiles of HNSCC patients were downloaded from The Cancer Genome Atlas (TCGA) database. The tumor microenvironment and immune response were estimated by cell type identification via estimating relative subset of known RNA transcripts (CIBERSORT) and immunophenoscore (IPS). The differential expression pattern based on human papillomavirus status was identified. A DEGs-based prognostic risk model was developed and validated. All statistical analyses were performed with R software (version 3.6.3).ResultsBy using the TCGA database, we identified DKK1, HBEGF, RNASE7, TNFRSF12A, INHBA, and IPIK3R3 as DEGs that were associated with patients’ overall survival (OS). Patients were stratified into the high- and low-risk subgroups according to a DEGs-based prognostic risk model. Significant difference in OS was found between the high- and low-risk patients (1.64 vs. 2.18 years, P = 0.0017). In multivariate Cox analysis, the risk model was an independent prognostic factor for OS (hazard radio = 1.06, 95% confidence interval [1.02–1.10], P = 0.004). More CD8+ T cells and regulatory T cells were observed in the low-risk group and associated with a favorable prognosis. The IPS analysis suggested that the low-risk patients possessed a higher IPS score and a higher immunoreactivity phenotype, which were correlated with better immunotherapy response.ConclusionCollectively, we established a reliable DEGs-based risk model with potential prognostic value and capacity to predict the immunophenotype of HNSCC patients.
Highlights
Squamous cell carcinomas, originating from the oral cavity, oropharynx, larynx, or hypopharynx, are collectively referred to as head and neck squamous cell carcinoma (HNSCC)
Patients were stratified into the high- and low-risk subgroups according to a differentially expressed genes (DEGs)-based prognostic risk model
Collectively, we established a reliable DEGs-based risk model with potential prognostic value and capacity to predict the immunophenotype of HNSCC patients
Summary
Squamous cell carcinomas, originating from the oral cavity, oropharynx, larynx, or hypopharynx, are collectively referred to as head and neck squamous cell carcinoma (HNSCC). About two-thirds of HNSCC patients are diagnosed at late stages with poor prognosis. Patients with locally advanced stage HNSCC are treated with surgery and postoperative radiotherapy. Targeted drugs, such as cetuximab, an epidermal growth factor receptor (EGFR)–specific antibody, have been utilized for HNSCC and reached a limited response rate, possibly due to its clinical heterogeneity (Licitra et al, 2011). Head and neck squamous carcinoma (HNSCC), characterized by immunosuppression, is a group of highly heterogeneous cancers. Immunotherapy exerts a promising influence on HNSCC, the response rate remains low and varies in assorted primary sites. This study aimed to develop a differentially expressed genes (DEGs)–based risk model to predict immunotherapy efficacy and stratify prognosis of HNSCC patients
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