Integrated Omic Analysis of Oropharyngeal Carcinomas Reveals Human Papillomavirus

HPV-positive oropharyngeal carcinoma (OPC) patients have superior outcomes relative to HPV-negative pa-tients, but the underlying mechanisms remain poorly un-derstood. We conducted a proteomic investigation of HPV-positive (n 27) and HPV-negative (n 26) formalin-fixed paraffin-embedded OPC biopsies to acquire insights into the biological pathways that correlate with clinical behavior. Among the 2,633 proteins identified, 174 were differentially abundant. These were enriched for proteins related to cell cycle, DNA replication, apoptosis, and im-mune response. The differential abundances of cortactin and methylthioadenosine phosphorylase were validated by immunohistochemistry in an independent cohort of 29 OPC samples (p 0.023 and p 0.009, respectively). An additional 1,124 proteins were independently corrobo-rated through comparison to a published proteomic da-taset of OPC. Furthermore, utilizing the Cancer Genome Atlas, we conducted an integrated investigation of OPC, attributing mechanisms underlying differential protein abundances to alterations in mutation, copy number, methylation, and mRNA profiles. A key finding of this integration was the identification of elevated cortactin oncoprotein levels in HPV-negative OPCs. These proteins might contribute to reduced survival in these patients via their established role in radiation resistance. Through in-terrogation of Cancer Genome Atlas data, we demon-strated that activation of the 1-integrin/FAK/cortactin/ JNK1 signaling axis and associated differential regulation of activator protein 1 transcription factor target genes are plausible consequences of elevated cortactin protein levels. Molecular & Cellular Proteomics 13: 10.1074