A Molecular Study Of HPV-associated Oropharyngeal Carcinoma With Bioinformatics Approach

Background:Oropharyngeal squamous cell carcinoma (OPSCC) is one of the most common head and neck cancers. Traditionally, tobacco smoking and alcohol consumption are major risk factors for OPSCC. In recent decades, human papilloma virus (HPV) has also emerged as a major etiological agent in OPSCC. Patients with HPV-positive OPSCC have distinct clinical characteristics and prognosis. Recent research from International Agency for Research on Cancer (IARC) suggested OPSCC patients with HPV-active status have a better prognosis than the ones with HPV-inactive status or HPV-negative status. However, the implication of HPV status in OPSCC remains unclear.Objectives:To analyze microarray data of HPV-active, HPV-inactive and HPV-negative OPSCC, and then construct and analyze PPI networks based on microarray data and protein database. Methods:1、The gene expression profiling of HPV-active, HPV-inactive and HPV-negative OPSCC was compared with normal oropharyngeal tissue using Limma package. The differentially expressed genes (DEGs) were identified respectively. GO (Gene Ontology) analysis and KEGG pathway analysis of DEGs was then conducted.2、The protein-protein interaction information was combined from HPRD, MINT and BioGRID.3、Three PPI networks were constructed for DEGs in each group. Clusters in these networks were identified and further analyzed by ClusterOne.Results:1、A total of184,482and543DEGs were identified in HPV-active, HPV-inactive and HPV-negative OPSCC group respectively. Functional analysis of DEGs showed that these DEGs were mainly enriched in "epidermal development","epidermal differentiation","cell adhesion","biological adhesion","extracellular matrix (ECM)" and "cytokines activity".2、Three PPI networks were constructed for corresponding DEGs. Through the cluster analysis, COL1A1was identified as hub protein in all the PPI networks. UBC and CEACAMs were identified as hub proteins in HPV-inactive and HPV-negative PPI networks.Conclusions1、The epidermal development and differentiation, cell adhesion, the change of ECM and the disturbance of cytokines activity might make contribution to the development of OPSCC. 2、 Comparing with HPV-active OPSCC, HPV-inactive OPSCC shared more common biomarkers with HPV-negative OPSCC.3、 COL1A1might be an important biomarker for OPSCC while UBC and CEACAMs might be important biomarkers for HPV-inactive and HPV-negative OPSCC.