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标题：Integrative Genomics and Transcriptomics Analysis Reveals Potential Mechanisms for Favorable Prognosis of Patients with HPV-Positive Head and Neck Carcinomas
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作者：Wensheng Zhang ; Andrea Edwards ; Zhide Fang 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2016
卷号：6
期号：1
DOI：10.1038/srep24927
语种：English
出版社：Springer Nature
摘要：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.