Department of Pathology, The First Affiliated Hospital of the Medical College, Shihezi University, Shihezi, China; Department of Pathology, Shihezi University School of Medicine, Shihezi, China.
Department of Pathology, The First People's Hospital of Changde City, Changde 415003, China.
Gene. 2020 Jan 10;723:144142. doi: 10.1016/j.gene.2019.144142. Epub 2019 Oct 4.
DNA methylation is an epigenetic alteration that may lead to carcinogenesis by silencing key tumor suppressor genes. Hypermethylation of the paired box gene 1 (PAX1) promoter is important in cervical cancer development. Here, PAX1 methylation levels were compared between Uyghur and Han patients with cervical lesions. Data on PAX1 methylation in different cervical lesions were obtained from the Gene Expression Omnibus (GEO) database, whereas data on survival and PAX1 mRNA expression in invasive cervical cancer (ICC) were retrieved from the Cancer Genome Atlas (TCGA) database. MassARRAY spectrometry was used to detect methylation of 19 CpG sites in the promoter region of PAX1, whereas gene mass spectrograms were drawn by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry. Human papillomavirus (HPV) 16 infection was detected by polymerase chain reaction. PAX1 methylation in high-grade squamous intraepithelial lesion (HSIL) and ICC was significantly higher than in normal tissues. PAX1 hypermethylation was associated with poor prognosis and reduced transcription. ICC-specific PAX1 promoter methylation involved distinct CpG sites in Uyghur and Han patients HPV16 infection in HSIL and ICC patient was significantly higher than in normal women (p < 0.05). Our study revealed a strong association between PAX1 methylation and the development of cervical cancer. Moreover, hypermethylation of distinct CpG sites may induce HSIL transformation into ICC in both Uyghur and Han patients. Our results suggest the existence of ethnic differences in the genetic susceptibility to cervical cancer. Finally, PAX1 methylation and HPV infection exhibited synergistic effects on cervical carcinogenesis.
DNA 甲基化是一种表观遗传改变，它可能通过沉默关键肿瘤抑制基因导致致癌作用。配对盒基因 1（PAX1）启动子的高甲基化在宫颈癌的发生发展中具有重要作用。本研究比较了维吾尔族和汉族宫颈病变患者 PAX1 甲基化水平。不同宫颈病变中 PAX1 甲基化的数据来自基因表达综合数据库（GEO），而浸润性宫颈癌（ICC）中 PAX1 甲基化和生存以及 PAX1mRNA 表达的数据则从癌症基因组图谱（TCGA）数据库中获得。采用 MassARRAY 质谱技术检测 PAX1 启动子区 19 个 CpG 位点的甲基化情况，并用基质辅助激光解吸电离飞行时间质谱法绘制基因质谱图。采用聚合酶链反应检测人乳头瘤病毒（HPV）16 感染情况。高级别鳞状上皮内病变（HSIL）和 ICC 中的 PAX1 甲基化明显高于正常组织。PAX1 高甲基化与不良预后和转录减少有关。ICC 中 PAX1 启动子的特异性甲基化涉及维吾尔族和汉族患者 HPV16 感染中不同的 CpG 位点，HSIL 和 ICC 患者中的 HPV16 感染明显高于正常女性（p<0.05）。本研究揭示了 PAX1 甲基化与宫颈癌发生发展之间的密切关系。此外，在维吾尔族和汉族患者中，不同 CpG 位点的高甲基化可能诱导 HSIL 向 ICC 转化。我们的研究结果提示，在宫颈癌的遗传易感性方面存在民族差异。最后，PAX1 甲基化和 HPV 感染对宫颈癌的发生具有协同作用。
