[关键词]
[摘要]
目的:卵巢癌是严重威胁女性健康的疾病,病死率居妇科恶性肿瘤之首。多药耐药是卵巢癌患者术后化疗失败的主要原因,而DNA甲基化则是卵巢癌多药耐药调控的重要机制,因此全面了解DNA甲基化对卵巢癌多药耐药的调控机制对于卵巢癌治疗和预后具有重要意义。通过PubMed数据库检索,笔者共提取了26个与卵巢癌多药耐药调控显著相关的DNA甲基化基因,系统整合分析了这些基因甲基化水平改变对卵巢癌耐药的影响及其分子调控机制。在所有26个基因中,至少一半以上的DNA甲基化基因直接或间接地通过调控细胞凋亡信号通路响应耐药调控,说明该信号通路可能是DNA甲基化基因行使其耐药生物学功能的主要方式。另外,分析这26个卵巢癌耐药相关甲基化基因与患者临床预后的关系,表明上述基因主要与不良预后相关。总之,深入探讨DNA甲基化基因与卵巢癌耐药和预后的潜在关系,对于充分认识DNA甲基化对卵巢癌耐药的调控及提高卵巢癌的疗效和改善预后具有一定的指导意义。
[Key word]
[Abstract]
Ovarian cancer is a malignant tumour that poses a serious threat to women's health. In most cases of ovarian cancer, drug resistance develops in the course of post-surgery chemotherapy. It has been well documented that DNA methylation is one of the important regulatory mechanisms underlying the development of multidrug resistance in ovarian cancer patients. However, the relationship between DNA methylation and drug resistance and clinical prognosis has yet to further understood. Through an electronic search of the PubMed database, we have identified 26 methylated genes that have been reported to be associated with the regulation of ovarian cancer drug resistance. Among these genes, at least half respond to ovarian cancer drug resistance by directly or indirectly regulating signaling pathways involved in cell apoptosis. Moreover, we have performed an integrated analysis of the relationship between these 26 methylated genes and the behaviour and prognosis of malignant ovarian cancer and have found that DNA methylation is primarily associated with poor prognosis. Herein in this review paper, we attempt to present the general information on the 26 identified methylated genes related to drug resistance, outline the putative molecular mechanisms through which DNA methylation affect drug resistance and discuss the possible strategies for reverse how the DNA methylation-induced drug resistance to improve prognosis in malignant ovarian cancer.
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[基金项目]
高等学校博士学科点专项科研基金资助项目(No. 20124503110003);广西科学研究与技术开发计划课题(No. 14124004);广西自然科技基金(No. 2014 jjAA40673)。