To Explore The Prognostic Model Of Apoptosis In Head And Neck Squamous Cell Carcinoma Based On Bioinformatics Technology

Objective:Squamous cell carcinoma of the head and neck is the sixth most prevalent tumor worldwide.Many HNS CCS are associated with classic causes such as smoking and alcohol consumption,and infection with human papillomavirus(HPV)results in clinically,genomic and immunologically distinct tumor subsets in the tonsil epithelium and tongue base.Hpv-negative tumors are associated with mutations in tobacco-associated genes,including TP53 and CDKN2A.In HPV-positive HNSCC,the viral genome of HPV is integrated into the host cell genome,resulting in the expression of E6 and E7 viral oncoproteins,followed by p53 degradation and Rb inactivation.HNSCC immune microenvironment changes are the changes of immune cell population,immune checkpoint and tumor microenvironment factors,which change the balance of the immune environment and facilitate immunosuppression,thus enabling tumors to evade immune surveillance.Immunotherapies,particularly those targeting the PD-1 receptor or its ligand PD-L1,including napemuzumab,wulliuzumab,attezumab,and devaruzumab,have shown significant efficacy in subpopulations of HNSCC patients.Trials are currently evaluating the efficacy of these drugs in combination with chemotherapy.While biomarkers such as PD-L1,PD-L2,and interferon-γ genes show potential as novel approaches to checkpoint inhibitor therapy,a deeper understanding of the genome and immune environment will allow us to better refine stratified treatment strategies and select which HNSCCS are most likely to benefit from these therapies.The molecular pathogenesis of HNSCC includes disturbances of cell cycle,intercellular signaling,cell differentiation and apoptosis.In addition to gene mutations,HNSCC changes include epigenetic changes,such as DNA methylation,histone modification,non-coding RNA activity,and RNA methylation.Some of them can promote the formation and progression of HNSCC tumor cells by controlling gene expression.Therefore,we seek new prognostic models that can be used as biomarkers for clinical monitoring of HNSCC and as therapeutic strate gies.Methods:To screen for differentially expressed apoptotic genes,we analyzed the expression levels of 161 apoptotic genes in tumor and paracancer tissues of head and neck squamous cell carcinoma from cancer Genome Atlas Database(TCGA).Next,gene body(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were performed to evaluate the potential molecular mechanisms of differentially expressed apoptotic genes in head and neck squamous cell carcinoma.Cox regression was used to establish the prognostic value of apoptotic genes.A prognostic risk model was developed to score patients,and kaplan-Meier(KM)curves were drawn to determine the prognostic value of the modelResults:Compared with normal tissues,35 highly up-regulated and 9 down-regulated apoptotic genes were screened in squamous cell carcinoma of head and neck.GO analysis showed that these 44 genes were indeed related to apoptosis function.KEGG analysis showed that these 44 genes were associated with MAPK,P53,TNF and PI3K-Akt signaling pathways,and Cox regression showed that 5 apoptotic genes(APP,BMF,CCNA1,CD38,SLC20A1)were associated with prognosis,thus obtained the prognostic model developed by this method.Patients were divided into low-risk and high-risk groups based on the median risk score.2-or 5-year survival was significantly higher in the low-risk group(P<0.0001).Risk models have better clinical efficacy than other clinical features.Conclusion:Based on the differential expression of apoptotic genes and head and neck squamous cell carcinoma,we established a new risk model for predicting prognosis in patients with head and neck squamous cell carcinoma.This model can be used to guide the individualized treatment of patients with squamous cell carcinoma of the head and neck and to predict and evaluate the effectiveness of new treatment methods.