基于生物信息学方法分析miR-3193及其甲基化在宫颈癌中的临床意义

Clinical Significance of miR-3193 and Its Methylation in Cervical Cancer Based on Bioinformatics

目的 评估miR-3193表达及其甲基化作为宫颈癌不良预后的生物标志物的可行性。方法 从The Cancer Genome Atlas (TCGA)数据库中获取宫颈癌患者的基因表达数据和相应的临床信息。通过生物信息学方法揭示宫颈癌患者miR-3193表达及甲基化与患者的临床特征与预后之间的关系。结果 miR-3193表达与宫颈癌临床分期、肿瘤大小呈正相关。Cox回归和Kaplan-Meier法证实miR-3193上调是宫颈癌不良预后的独立危险因素。miR-3193受DNA甲基化负调控,miR-3193低甲基化提示宫颈癌患者预后不良。功能富集分析显示miR-3193可能通过调控TGF-β和PI3K-Akt等信号通路参与宫颈癌发病机制。通过CMap分析筛选出对宫颈癌有潜在抑制作用的4种小分子药物(阿霉素、喜树碱、GW-8510和阿扎胞苷)。结论 miR-3193低甲基化可能是宫颈癌不良预后的生物标志物。

Objective To evaluate the feasibility of miR-3193 expression and its methylation as a biomarker for poor prognosis of cervical cancer.Methods The gene expression data and corresponding clinical information of cervical cancer patients were obtained from The Cancer Genome Atlas(TCGA) database. The relationship between miR-3193 expression and methylation in cervical cancer patients and their clinical characteristics and prognosis was revealed by bioinformatics.Results The expression of miR-3193 was positively correlated with the clinical stage and tumor size of cervical cancer. Cox regression and Kaplan-Meier method confirmed that up-regulation of miR-3193 was an independent risk factor for poor prognosis of cervical cancer. miR-3193 was negatively regulated by DNA methylation, and hypomethylation of miR-3193 indicates poor prognosis in patients with cervical cancer. Functional enrichment analysis showed that miR-3193 may regulate TGF-β And PI3K-Akt signal pathways were involved in the pathogenesis of cervical cancer. Four small-molecular drugs(doxorubicin, camptothecin, GW-8510 and azacytidine) with potential inhibitory effects on cervical cancer were screened through CMap analysis.Conclusion miR-3193 and hypomethylation may be biomarkers for poor prognosis of cervical cancer.