Gao Dongmei, Zhang Yuanyuan, Zhu Mingyue, Liu Shuang, Wang Xinling
Department of Gynecology, Cancer Hospital, Xinjiang Medical University, Urumqi, 830011, China.
PLoS One. 2016 Oct 20;11(10):e0164701. doi: 10.1371/journal.pone.0164701. eCollection 2016.
The study aimed to investigate the state of human papillomavirus (HPV) infection in patients with cervical cancer in the Uyghur population in China and to identify miRNA as biomarker for cervical cancer and HPV infection. We also performed genotyping to determine the variation in the types of HPV. Using microRNA (miRNA) microarray technology, differential miRNA expression between HPV-infected cervical cancer and uninfected normal cervical tissues was determined; the microarray results were verified by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) using 20 samples of both the tissues. The infection rate of HPV in patients with cervical cancer was 96.7% (29 of 30), and the main subtype identified was HPV16 (29 of 29). HPV16 integration assay demonstrated that the majority of infectious cases were of the integrated form (26 of 29). Analysis of 140 miRNAs demonstrated greater than two-fold change in miRNA expression in HPV-infected cervical cancer tissue as compared to that in uninfected cervical tissue. The qRT-PCR analysis verified that the expression of miR-15a-5p, miR-17-5p, miR-20a-5p, miR-21-5p, miR-96, miR-106b-5p, and miR-3653 was higher, while the expression of miR-497-5p was lower in cancer tissues than in normal tissues. The results demonstrate significant changes in miRNA expression in cervical cancer tissues associated with HPV infection as compared to that in normal tissues. These molecular markers may be useful for an early diagnosis and prognosis of cervical cancer in specific human populations.
本研究旨在调查中国维吾尔族宫颈癌患者中人乳头瘤病毒(HPV)的感染状况,并确定miRNA作为宫颈癌和HPV感染的生物标志物。我们还进行了基因分型以确定HPV类型的变异。使用微RNA(miRNA)微阵列技术,确定了HPV感染的宫颈癌组织与未感染的正常宫颈组织之间miRNA表达的差异;使用两种组织的20个样本,通过定量逆转录聚合酶链反应(qRT-PCR)验证了微阵列结果。宫颈癌患者的HPV感染率为96.7%(30例中的29例),鉴定出的主要亚型为HPV16(29例中的29例)。HPV16整合分析表明,大多数感染病例为整合形式(29例中的26例)。对140种miRNA的分析表明,与未感染的宫颈组织相比,HPV感染的宫颈癌组织中miRNA表达变化超过两倍。qRT-PCR分析证实,癌组织中miR-15a-5p、miR-17-5p、miR-20a-5p、miR-21-5p、miR-96、miR-106b-5p和miR-3653的表达较高,而miR-497-5p的表达低于正常组织。结果表明,与正常组织相比,HPV感染的宫颈癌组织中miRNA表达有显著变化。这些分子标志物可能有助于特定人群宫颈癌的早期诊断和预后评估。