Integrative Genomics and Transcriptomics Analysis Reveals Potential Mechanisms for Favorable Prognosis of Patients with HPV-Positive Head and Neck Carcinomas.
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.
Department of Computer Science, Xavier University of Louisiana, 1 Drexel Drive, New Orleans LA 70125, USA.
Wensheng
W
Zhang
Department of Computer Science, Xavier University of Louisiana, 1 Drexel Drive, New Orleans LA 70125, USA.
Andrea
A
Edwards
Biostatistics Program, School of Public Health, Louisiana State University Health Sciences Center, New Orleans, LA, 70112, USA.
Zhide
Z
Fang
Tulane Health Sciences Center, Tulane Cancer Center, Tulane University, 1700 Tulane Ave, New Orleans, LA 70112, USA.
Erik K
EK
Flemington
Department of Computer Science, Xavier University of Louisiana, 1 Drexel Drive, New Orleans LA 70125, USA.
Kun
K
Zhang
D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D020869:Gene Expression Profiling; D023281:Genomics; D006258:Head and Neck Neoplasms / Q000473:pathology*; D006801:Humans; D030361:Papillomavirus Infections / Q000150:complications*; D011379:Prognosis