Integrative Genomics and Transcriptomics Analysis Reveals Potential Mechanisms for Favorable Prognosis of Patients with HPV-Positive Head and Neck Carcinomas.
Integrative Genomics and Transcriptomics Analysis Reveals Potential Mechanisms for Favorable Prognosis of Patients with HPV-Positive Head and Neck Carcinomas.
复制标题
DOI：
10.1038/srep24927
复制
发表时间：
2016-04-25
影响因子：
4.6
通讯作者：
Zhang K
中科院分区：
文献类型：
--
作者：
Zhang W;Edwards A;Fang Z;Flemington EK;Zhang K
HPV阳性的头颈部鳞状细胞癌（HNSCC）患者通常比HPV阴性的病例有更好的预后，但其潜在的机制仍远未得到很好的理解。我们通过对癌症基因组图谱发布的临床注释的多组学HNSCC数据的综合分析来研究这个问题。作为验证性结果，我们发现：（1）突变型TP 53和HPV感染的共同发生是罕见的;（2）无论HPV状态如何，野生型TP 53的HNSCC都意味着患者有良好的生存机会，并且比基因突变负荷的HNSCC具有更少的全基因组体细胞突变。我们的分析进一步导致了一些新的观察结果。其中包括：（1）与正常组织样本和HPV阴性病例相比，HPV阳性肿瘤中参与“DNA错配修复”途径的基因上调，因此构成了鉴定HPV感染的强预测特征;（2）HPV感染可破坏HPV阴性肿瘤中的一些调节性miRNA-mRNA相关性。根据这些结果，我们提出了HPV阳性HNSCC患者良好临床结局的假设。也就是说，HPV基因组的复制和/或其侵入癌细胞的基因组可能会增强DNA修复机制，这反过来又限制了致死性体细胞突变的积累。
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.
影响因子：
3.7
作者：
Zhang W;Edwards A;Flemington E;Zhang K
通讯作者：
Zhang K