Aim: Head and neck squamous cell carcinoma (HNSCC) ranks seventh in incidence among the most common types of cancer worldwide. Although smoking and drinking are risk factors for HNSCC, the specific causes of, and molecular mechanisms underlying, of HNSCC have not been identified. Despite improvements in tumor treatment technology over the last 40 years, the prognosis of patients with HNSCC has not changed significantly. Therefore, to improve HNSCC treatment strategies and for early diagnosis, it is important to study its pathogenesis, and to identify prognostic markers for it.
Materials and methods: We used an integrated bioinformatics approach to identify key pathogenic and prognostic genes involved in HNSCC and to reveal the potential underlying molecular mechanisms. The expression profiles of the GSE6631 and GSE107591 datasets were downloaded from the Gene Expression Omnibus (GEO) database, and the tertiary RNA-sequencing dataset of HNSCC and corresponding clinical information were downloaded from The Cancer Genome Atlas (TCGA). These three datasets were integrated to identify differentially expressed genes (DEGs), and DEGs were analyzed using bioinformatic tools, including R packages.
Results: We identified 83 DEGs among these datasets. Gene Ontology analysis showed that the biological functions of the identified DEGs are primarily associated with regulating extracellular signal cascades, epidermis development, adhesion, and other tumor cytology behaviors. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that these DEGs were mainly involved in the PI3K-Akt, human papillomavirus infection, and IL-17 signaling pathways. A protein–protein interaction network was constructed to reveal the 20 most closely related genes among the DEGs.
Conclusion: Four key genes in the network (PLAU, SERPINE1, SPP1, and MMP1) were demonstrated to have prognostic relevance based on their significant associations with survival in patients with HNSCC. We verified the high expression of SERRPINE1 in hypopharyngeal carcinoma cell lines by qRT-PCR and Western blotting.
Clinical significance: Our findings would help elucidate the molecular mechanisms underlying the development and provide the possibility to improve the prognosis of HNSCC.