摘要
目的探讨难治性卵巢上皮癌耐药相关microRNA(miRNA),并预测其调控的靶基因,为进一步进行卵巢上皮癌耐药相关生物学通路研究提供基础。方法收集接受满意肿瘤细胞减灭术的100例Ⅱb~Ⅲc期卵巢上皮癌患者的一般资料和组织学标本,根据术后化疗效果将患者分为铂类敏感组(n=91)和难治性卵巢癌组(n=9),每组各选取3例患者使用Taq Man Real-time PCR microRNA Array进行分析,得出差异表达的miRNA。根据靶基因预测网站的分析、miRNA及其靶基因在肿瘤中的研究,筛选出目标miRNA作为区分难治性卵巢癌组与铂类敏感组的标志物以待进一步研究。结果 miRNA表达谱芯片得到两组差异表达的miRNA共118个,其中难治性卵巢癌组与铂类敏感组相比,表达降低的miRNA有42个,表达升高的miRNA有76个。综合现有文献及靶基因预测网站分析,选取6个miRNA作为区分难治性卵巢癌组与铂类敏感组的目标miRNA。与铂类敏感组相比,miRNA-21和miRNA-27a在难治性卵巢癌组中表达明显升高(P﹤0.001),miRNA-100、miRNA-770-5p、miRNA-200c和miRNA-497在难治性卵巢癌组中表达降低(P﹤0.05)。结论 miRNA-21等118个miRNA可能与卵巢上皮癌耐药相关,miRNA-21、miRNA-27a的升高及miRNA-100、miRNA-770-5p、miRNA-200c、miRNA-497的降低可能提示卵巢上皮癌原发耐药。
Objective To investigate the primary chemoresistance-related microRNA（miRNA） in refractory epithelial ovarian cancer, to lay a foundation for further study of miRNA related biological pathways. Method Clinical profile and tissue samples of 100 cases of epithelial ovarian cancer in FIGO stage IIb to IIIc treated with optimal cytoreductive surgery and paclitaxel plus carboplatin chemotherapy were collected. Based on postoperative chemotherapy responses, the patients were stratified as chemosensitive group and chemoresistant group. 3 patients in each group were selected and analyzed using Taq Man Real-time PCR miRNA Array analysis to identify significantly expressed miRNA. Based on the prediction of target gene and analysis of miRNA and its target genes in tumor, the target miRNA was screened as distinguished biomarkers for differentiating patients with high platinum-sensitivity and refractory disease. Result Taq Man Real-time PCR miRNA Array identified 118 significantly expressed miRNA. 76 miRNA were highly expressed and 42 were with lower expression in patients with refractory disease compared to those with high platinum-sensitivity. According to the existing literature and target gene prediction analysis, 6 miRNA were screened as the target miRNA to differentiate patients with refractory disease or with high platinum-sensitivity. Compared with high sensitivity group, the expression of miR-21 and miR-27 a were significantly increased（P〈0.001） and the expression of miR-100, miR-770-5p, miR-200 c and miR-497 were significantly lower（P〈0.05） in the refractory disease group. Conclusion The 118 miRNA screened by Taq Man Real-time PCR miRNA Array may be associated with drug resistance in epithelial ovarian cancer. The high expression of miRNA-21 and miRNA-27 a, low expression of miRNA-100, miRNA-770-5p, miRNA-200 c, and miRNA-497 may indicate the primary chemoresistance in epithelial ovarian cancer.
作者
胡金龙
韩倩
杨红杰
陈雪姣
付蕾
仓顺东
HU Jinlong;HAN Qian;YANG Hongjie;CHEN Xuejiao;FU Lei;CANG Shundong(Department of Oncology;Department of Radiotherapy, He＇nan Provincial People＇s Hospital, Zhengzhou 450003, He＇ nan, China)
出处
《癌症进展》
2017年第8期886-890,共5页
Oncology Progress
基金
河南省医学科技攻关项目(201602218)
