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目的:研究维吾尔族妇女宫颈病变与降钙素相关肽α(calcitonin-related polypeptide alpha,CALCA)基因启动子区CpG位点甲基化的关系,进一步揭示宫颈癌组织中该基因表达调控的表观遗传学机制。方法:收集维吾尔族妇女宫颈病变患者手术切除或活检组织标本50例,其中宫颈鳞癌(cervical squamous cell carcinoma,CSCC)25例、宫颈内上皮内瘤样变(cervical intraepithelial neoplasia,CIN)9例及慢性宫颈炎16例,应用Sequenom MassARRAY甲基化DNA定量分析平台,对组织DNA的CALCA基因启动子区CpG位点进行甲基化水平的定量分析。结果:宫颈炎、CIN和CSCC组织中CALCA基因启动子区CpG片段甲基化率分别为0.22、0.26和0.33,经统计学分析,CSCC与CIN以及CSCC与宫颈炎之间均有显著差异(P<0.05)。从单一CpG位点角度分析,CSCC与宫颈炎组织CpG-2、CpG-3、CpG-9.10.11和CpG-12等6个CpG位点甲基化率均有显著差异(P<0.05)。结论:CALCA基因启动子甲基化与维吾尔族妇女宫颈癌发生密切相关,其中特定CpG位点甲基化水平变化可能成为宫颈癌早期诊断的分子标志物。
Objective: To investigate the relationship between cervical lesions and methylation of CpG locus of calcitonin-related polypeptide alpha (CALCA) promoter in Uyghur women and further reveal the expression of this gene in cervical cancer Genetics mechanism. Methods: Fifty cases of surgical or biopsy specimens of cervical lesions were collected from Uighur women, including 25 cases of cervical squamous cell carcinoma (CSCC), 9 cases of cervical intraepithelial neoplasia (CIN) and Chronic cervicitis in 16 cases, the use of Sequenom MassARRAY methylation quantitative DNA analysis platform, the organization of DNA CALCA gene promoter CpG site methylation level quantitative analysis. Results: The methylation rates of CpG fragments in the promoter region of CALCA gene in cervicitis, CIN and CSCC were 0.22, 0.26 and 0.33, respectively. Statistical analysis showed significant differences between CSCC and CIN and between CSCC and cervicitis (P <0.05). From the perspective of single CpG locus, the methylation rates of CpG-2, CpG-3, CpG-9.10.11 and CpG-12 in CSCC and cervicitis were significantly different (P <0.05). Conclusion: The promoter methylation of CALCA gene is closely related to the occurrence of cervical cancer in Uighur women. The change of methylation level of specific CpG loci may become a molecular marker for early diagnosis of cervical cancer.