Title

Integrative Genomics and Transcriptomics Analysis Reveals Potential Mechanisms for Favorable Prognosis of Patients with HPV-Positive Head and Neck Carcinomas

Funding Source

National Institutes of Health, National Human Genome Research, National Cancer Institute

Grant Number

911NF-15-1-0510, 5R01AI106676,5R01AI101046, 2G12MD007595, 1U54GM104940

Department

Department of Physics and Computer Science - Dual Degree Engineering

Document Type

Article

Publication Date

4-25-2016

Abstract

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.

Comments

DOI: 10.1038/srep24927.

Funding text

This publication was made possible by funding from the NIH NIMHD-RCMI grant #2G12MD007595, the DOD ARO grant #W911NF-15-1-0510 and the Louisiana Cancer Research Consortium (LCRC). EKF was supported by the NIH grants 5R01AI101046 and 5R01AI106676. ZF was supported by the NIH NIGMS grant 1U54GM104940 which funds the Louisiana Clinical and Translational Science Center of Pennington Biomedical Research Center. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH, DOD or LCRC. The analyses presented here are based upon the data published by The Cancer Genome Atlas (TCGA) managed by the NCI and NHGRI. Information regarding TCGA can be found at http://cancergenome.nih.gov.ezproxy.xula.edu We are also grateful to the anonymous reviewers for their valuable comments.

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