Analysis of key genes and signal pathways of human papilloma virus-related head and neck squamous cell carcinoma

Abstract

Objective: To explore differentially expressed genes (DEG) and pathways between human papilloma virus (HPV) positive and negative head and neck squamous cell carcinoma (HNSCC) and to search gene targets for diagnosis and treatment of HPV-related HNSCC. Methods: HPV-related HNSCC expression profile chips of GSE3292 (including 8 HPV-positive and 28 HPV-negative HNSCC tissues, of which 15 collected from oral cavity cancer, 9 from oropharyngeal cancer, 9 from laryngeal cancer and 3 from hypopharyngeal cancer) were selected from Gene Expression Omnibus (GEO) database of National Center for Biotechnology Information and DEG were screened out using Gene-Cloud of Biotechnology Informs (GCBI). Gene ontology and pathway enrichment analysis were performed using DAVID and protein-to-protein interaction (PPI) network was constructed by STRING. Hub genes were identified by Cytoscape and then performed pathway enrichment analysis. Finally, expression differences of hub genes in the cancer genome atlas (TCGA) database were checked using UALCAN. Results: Five hundred and seventy-three DEG were screened out from more than 25 000 genes detected in the chips including 539 up-regulated genes and 34 down regulated ones. Twenty-seven hub genes including cyclin-dependent kinases 1(CDK1), proliferating cell nuclear antigen (PCNA), minichromosome maintenance proteins (MCM) family (MCM2, MCM3, MCM6 and MCM7), replication factor C subunit 4 (RFC4) and kinesin family member 11 (KIF11) were identified after two rounds of Cytoscape screening. Gene ontology and pathway analysis showed that DEG were mainly distributed in chromosome, nucleoplasm, nuclear lumen and membrane-enclosed lumen and participated in biological processes such as DNA replication, DNA metabolism, cell cycle and cell division, and also 6 major signaling pathways centered on p53 signaling pathway （P<0.01）. All hub genes were expressed differently between HPV-positive and negative HNSCC in TCGA database（P<0.01）. Conclusions: Hub genes including CDK1, PCNA, MCM family (MCM2, MCM3, MCM6 and MCM7) act as an important part on HPV-induced HNSCC and the p53 pathway is the key of this process and plays different regulatory roles between two subtypes of HNSCC. CDK1, MCM7 and RFC4 are expected to be potential treatment targets for HPV-positive HNSCC while MCM2, MCM3, PCNA and KIF11 may be employed as biomarkers for diagnosis and prognosis.