Zhou Ran, Chen Zhuo, Xiao Zuo-Run, Wang Shou-Li, Rong Chao
Department of Pharmacy, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Department of Pathology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Front Oncol. 2021 Oct 21;11:753102. doi: 10.3389/fonc.2021.753102. eCollection 2021.
Persistent high-risk HPV infection drives tumorigenesis in various human malignancies, including cervical, oropharyngeal, anal, and vulvar carcinomas. Although HPV-related tumors arise in several different sites, they share many common genetic and epigenetic events. Complex and heterogeneous genomic aberrations and mutations induced by high-risk HPV contribute to the initiation and progression of cervical cancer (CC). However, the associations between high-risk HPV infection and DNA methylation have not been clearly investigated. In the present study, HPV-related gene promoter methylation signature was comprehensively analyzed using multiple interactive platforms. CC patients were successfully classified into high-risk and low-risk groups with significant differences in clinical outcomes based on the HPV-related gene promoter methylation signature. Moreover, the protein levels of ALDH1A2 and clinical prognostic value were confirmed in the CC patients cohort. In summary, our study provides compelling evidence that HPV-related gene promoter methylation signature serves as a strong prognostic signature for CC patients. Clinical investigations in large CC patient cohorts are greatly needed to pave the way to implement epigenetic biomarkers into better clinical management.
持续性高危型人乳头瘤病毒（HPV）感染会引发多种人类恶性肿瘤的肿瘤发生，包括宫颈癌、口咽癌、肛门癌和外阴癌。尽管HPV相关肿瘤出现在几个不同部位，但它们有许多共同的遗传和表观遗传事件。高危型HPV诱导的复杂且异质性的基因组畸变和突变促成了宫颈癌（CC）的发生和发展。然而，高危型HPV感染与DNA甲基化之间的关联尚未得到明确研究。在本研究中，使用多个交互式平台对HPV相关基因启动子甲基化特征进行了全面分析。基于HPV相关基因启动子甲基化特征，CC患者被成功分为高危组和低危组，两组临床结局有显著差异。此外，在CC患者队列中证实了醛脱氢酶1A2（ALDH1A2）的蛋白水平及临床预后价值。总之，我们的研究提供了令人信服的证据，表明HPV相关基因启动子甲基化特征可作为CC患者的有力预后特征。非常需要在大型CC患者队列中进行临床研究，为将表观遗传生物标志物应用于更好的临床管理铺平道路。
