Dong Yuling, Tan Qiufen, Tao Lin, Pan Xiaolin, Pang Lijuan, Liang Weihua, Liu Wei, Zhang Wenjie, Li Feng, Jia Wei
Department of Pathology, Shihezi University School of Medicine Shihezi, China.
Department of Pathology, The Sixth People's Hospital of Huizhou City Guangdong, China.
Int J Clin Exp Pathol. 2015 Feb 1;8(2):1844-54. eCollection 2015.
Tissue factor pathway inhibitor 2 (TFPI2) is a Kunitz-type serine proteinase inhibitor, which plays an important role in the etiology of human malignancies. DNA methylation is a common epigenetic modification of the genome that is involved in regulating many cellular processes. In addition to human papilloma virus (HPV) infection, DNA methylation may play a role in the carcinogenesis of cervical cancer. Methylation of 22 CpG sites in the promoter region of the TFPI2 gene was detected by MassARRAY spectrometry and a gene mass spectrogram was drawn using MALDI-TOF MS. HPV16 was detected by PCR. We show that aberrant methylation of TFPI2 is present in a higher proportion of invasive cervical carcinoma (ICC) clinical samples as compared to normal cervical samples in Uygur and Han. Across the four pathologic lesions of the progression of cervical cancer, ICC showed the highest level of aberrant methylation, and with a stronger correlation between CpG site and lesion grade in Uygur than in Han. Moreover, a difference in TFPI2 methylation between Uygur patients positive and negative for HPV16 infection was observed at CpG_6 (P = 0.028) and CpG_15 (P = 0.007). Altogether, these results indicate that DNA methylation of TFPI2 may play an important role in the carcinogenesis of cervical cancer and that the differential methylation of TFPI2 may at least partially explain the disparity in cervical cancer incidence between Uygur and Han women.
组织因子途径抑制物2（TFPI2）是一种库尼兹型丝氨酸蛋白酶抑制剂，在人类恶性肿瘤的病因学中起重要作用。DNA甲基化是基因组常见的表观遗传修饰，参与调控许多细胞过程。除人乳头瘤病毒（HPV）感染外，DNA甲基化可能在宫颈癌的致癌过程中发挥作用。采用MassARRAY质谱分析法检测TFPI2基因启动子区域22个CpG位点的甲基化情况，并使用基质辅助激光解吸电离飞行时间质谱（MALDI-TOF MS）绘制基因质谱图。通过PCR检测HPV16。我们发现，与维吾尔族和汉族的正常宫颈样本相比，浸润性宫颈癌（ICC）临床样本中TFPI2的异常甲基化比例更高。在宫颈癌进展的四个病理病变阶段中，ICC的异常甲基化水平最高，且维吾尔族中CpG位点与病变分级之间的相关性比汉族更强。此外，在CpG_6（P = 0.028）和CpG_15（P = 0.007）位点观察到HPV16感染阳性和阴性的维吾尔族患者之间TFPI2甲基化存在差异。总之，这些结果表明TFPI2的DNA甲基化可能在宫颈癌的致癌过程中起重要作用，且TFPI2的差异甲基化可能至少部分解释了维吾尔族和汉族女性宫颈癌发病率的差异。
