Integrative Genomics and Transcriptomics Analysis Reveals Potential Mechanisms for Favorable Prognosis of Patients with HPV-Positive Head and Neck Carcinomas
National Institutes of Health, National Human Genome Research, National Cancer Institute
911NF-15-1-0510, 5R01AI106676,5R01AI101046, 2G12MD007595, 1U54GM104940
Department of Physics and Computer Science - Dual Degree Engineering
Patients with HPV-positive head neck squamous cell carcinomas (HNSCC) usually have a better prognosis than the HPV-negative cases while the underlying mechanism remains far from being well understood. We investigated this issue by an integrative analysis of clinically-annotated multi-omics HNSCC data released by the Cancer Genome Atlas. As confirmatory results, we found: (1) Co-occurrence of mutant TP53 and HPV infection was rare; (2) Regardless of HPV status, HNSCCs of wild-type TP53 implied a good survival chance for patients and had fewer genome-wide somatic mutations than those with a mutation burden on the gene. Our analysis further led to some novel observations. They included: (1) The genes involved in "DNA mismatch repair" pathway were up-regulated in HPV-positive tumors compared to normal tissue samples and HPV-negative cases, and thus constituted a strong predictive signature for the identification of HPV infection; (2) HPV infection could disrupt some regulatory miRNA-mRNA correlations operational in the HPV-negative tumors. In light of these results, we proposed a hypothesis for the favorable clinical outcomes of HPV-positive HNSCC patients. That is, the replication of HPV genome and/or its invasion into the genomes of cancer cells may enhance DNA repair mechanisms, which in turn limit the accumulation of lethal somatic mutations.
Zhang, W.; Edwards, Andrea; Fang, Z.; Flemington, E. K.; and zhang, kun, "Integrative Genomics and Transcriptomics Analysis Reveals Potential Mechanisms for Favorable Prognosis of Patients with HPV-Positive Head and Neck Carcinomas" (2016). Faculty and Staff Publications. 63.