卵巢癌中microRNA基因多态与化疗耐药关系的研究

The mortality of ovarian cancer accounts for the first place in gynecological malignancy. Drug resistance is the main cause for the failure of treatment. However, No effective predictor exists clinically. As we know, single nucleotide polymorphism (SNP) is the most common of natural variation of the sequence, which is the main factor to determine the difference of drug reaction. Meanwhile, more and more evidence indicate that microRNAs, a kind of noncoding small RNA, can regulate the reaction to antineoplastic drugs. We hypothesis that there were functional SNPs exist in the drug resistance related microRNA in ovarian cancer.These polymorphisms may influence the effect of chemotherapy, and participate the process of drug resistance though target genes. We have screened microRNA defferential expression in tissue specimens of ovarian cancer between the drug sensitive group and the drug resistant group. We further plan to prospectively investigate the realationship between microRNA and effect of chemotherapy, using high thoughput method to detect nucleic acids and multiple genes analysis. Moreover, we will identify those functional microRNA polymorphisms and study their function on cell or tissue level. Those might provide theory for clinical prediction and personalized chemotherapy. In a word, this might help to elucidate mechanism of drug resistance in ovarian cancer, and provide new treatment.It is worth of theoretical and practical significance.

卵巢癌死亡率居妇科恶性肿瘤首位，而化疗耐药是其治疗失败的主要原因，临床上缺少有效的预测指标。基因多态是序列的自然变异，以单核苷酸多态最常见，是决定药物反应性差异的主要因素。越来越多证据还表明肿瘤对药物的反应受到一种非编码小分子RNA-microRNA（miRNA）的调控。我们假设与卵巢癌耐药相关的miRNA存在功能性基因多态，会影响肿瘤的化疗效果，并通过相应靶基因参与卵巢癌耐药机制。本项目应用miRNA芯片已成功在卵巢癌化疗敏感组和耐药组的肿瘤组织中筛选出miRNA的差异表达谱，拟进一步采用高通量核酸检测和多基因联合分析方法前瞻性研究相关miRNA基因多态与卵巢癌化疗疗效的关系，并从细胞和组织水平上系统的对这些miRNA基因多态进行鉴定和功能研究，为卵巢癌临床预测耐药和个体化化疗提供理论依据。这有助于进一步阐明卵巢癌耐药机制，并可能为攻克卵巢癌提供新的途径和方法，具有重大的理论和实用价值。

近年，卵巢癌发病呈增加趋势，其死亡率居妇科恶性肿瘤首位，而化疗耐药是其治疗失败的主要原因，临床上缺少有效的预测指标。基因多态是序列的自然变异，以单核苷酸多态最常见，是决定疾病易感性和药物反应性差异的主要因素。我们通过分子遗传学的方法，研究了遗传变异与卵巢癌发生发展、治疗及预后的关联，发现了存在一个miRNA基因多态与卵巢癌的化疗效果密切关联。进一步的研究还发现一个凋亡相关基因多态也与卵巢癌耐药相关。表型检测结果还显示错配修复基因存在着一个与卵巢癌的发生相关的基因多态。这些遗传变异在功能试验中得到了验证。上述研究为卵巢癌的筛查、治疗提供了科学依据。