Identification of differentially expressed genes in HPV-positive and HPV-negative oropharyngeal squamous cell carcinomas

Abstract

Human papillomaviruses (HPVs) have been implicated in the pathogenesis of a subset of squamous cell carcinoma of the head and neck (SCCHN). The goal of this study was to compare the cellular gene expression profiles of HPV-positive and HPV-negative oropharyngeal carcinomas with those of the normal oral epithelium. Using Affymetrix Human U133A GeneChip, our results showed that 397 genes were differentially expressed in HPV-positive SCCHN compared to the normal oral epithelium. The upregulated genes included those involved in cell cycle regulation ( CDKN2A), cell differentiation ( SFRP4) and DNA repair ( RAD51AP1), while the downregulated genes included those involved in proteolysis ( PRSS3). We also found 162 differentially expressed genes in HPV-negative SCCHN compared to the normal oral mucosa. The upregulated genes included those involved in cell proliferation ( AKR1C3) and transcription regulation ( SNAPC1), while downregulated genes included those involved in apoptosis ( CLU) and RNA processing ( RBM3). Our studies also identified a subgroup of 59 differentially expressed genes in HPV-positive SCCHN as compared to both HPV-negative SCCHN and normal oral tissues. Such upregulated genes included those involved in nuclear structure and meiosis ( SYCP2), DNA repair ( RFC5), and transcription regulation ( ZNF238). Genes involved in proteolysis ( KLK8) and signal transduction ( CRABP2) were found to be downregulated in HPV-positive SCCHN. The results of GeneChip experiments were validated by quantitative real-time RT-PCR analysis of a few representative genes. Our results reveal specific gene expression patterns in HPV-positive and HPV-negative oropharyngeal squamous carcinomas that may serve as potential biomarkers for the development of SCCHN.