Exploring the immune characteristics of HPV-positive HNSCC patients based on bioinformatics research and identifying SERPINE1 as a key factor affecting the prognosis of HNSCC patients with HPV

Abstract

Background Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide with an increasing trend of its incidence. Human papillomavirus (HPV) positive HNSCC patients generally have a favorable survival and a promising responsiveness to radiotherapy, chemoradiotherapy and checkpoint blockades. However, the immunological characteristics of HPV-positive patients and the reasons for their better prognosis have not yet been fully elucidated. Methods Two public datasets (GSE3292 and TCGA-HNSC) originate from the NCBI Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas. We first analyzed the tumor immune infiltration level and tumor mutation load of HPV + HNSCN patients in TCGA-HNSC. Subsequently, differentially expressed genes were analyzed by the R software limma package. Besides, we use weighted gene co-expression network analysis (WGCNA) to identify the gene modules that may be most relevant to HPV + HNSCC. Gene set enrichment analysis (GSEA) was performed using the differentially expressed genes, all the genes that may be most relevant to HPV that we are interested in HPV + HNSCC were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genomes (KEGG). Furthermore, a protein-protein interaction (PPI) network was constructed to investigate hub genes. Immunohistochemistry was used to verify the selected gene. Drugs and molecular compounds that could interact with hub genes were predicted using the DGIdb. Results We found that compared with HPV-HNSCC, HPV + HNSCC patients have higher immune cell scores. After integrating significantly differentially expressed genes from different datasets and key genes related to HPV modules, we found that 10 genes represented by SERPINE1 may be closely associated with HPV + HNSCC and immune infiltration. The results of immunohistochemistry showed that the expression of this gene was significantly reduced in HPV + HNSCC patients, suggesting that our gene may be a key factor influencing the prognosis of HPV + HNSCC patients. Conclusions We found the downregulation of a series of genes represented by SERPINE1 may be related to better prognosis in HPV + HNSCC patients. Research on the SERPINE1 gene pathway may bring new treatment methods to HNSCC emphasizing its implements in the therapeutic choices of HPV-negative HNSCC patients, the majority and the poor outcome population of HNSCC.