【摘要】 目的筛选在卵巢癌演进过程中起重要作用的microRNA(miRNA),检测关键miRNA与临床病理及预后的联系,找出与卵巢浆液性癌预后相关的miRNA。方法 miRNA芯片技术分别检测6例Ⅰ期浆液性癌,4例Ⅲ期浆液性癌的miRNA表达谱差异。统计分析,从中挑选4个miRNA,miR-510、miR-509-5p、miR-508-3p、miR-483-5p,采用实时定量PCR方法检测其在16例Ⅰ期浆液性癌、35例Ⅲ期浆液性癌中的表达,对比分析。收集验证组患者的临床病理及预后资料。将miRNA实时定量PCR结果分为高表达组和低表达组,分别统计各miRNA的表达与临床病理参数及预后的关系。结果 miRNA芯片技术分析了768个miRNA在Ⅰ期和Ⅲ期的表达谱,其中26个miRNA在两组中的表达具有显著差异(P<0.05),差别在两倍以上。对比Ⅰ期,Ⅲ期中6个miRNA上调,20个miRNA下调。实时定量PCR结果与miRNA芯片结果一致,显示miR-510、miR-509-5p、miR-508-3p在Ⅰ期卵巢癌标本中显著高于Ⅲ期浆液性癌,miR-483在Ⅰ期中表达显著低于Ⅲ期浆液性卵巢癌。但4个miRNA的表达与其他临床病理参数无关。生存分析发现miR-510、miR-509-5p二者与预后有关,高表达组的预后显著优于低表达组。结论 miRNA参与卵巢浆液性癌的发展,miR-510及miR-509-5p可能在卵巢癌的侵袭和转移中起作用,有望成为预测卵巢癌预后的分子标记物。更多还原

【Abstract】 Objective One of the best prognostic predictors for patients with epithelial ovarian cancer is the clinical pathological stage at diagnosis. The goal of this study is to develop and validate a gene expression profile that can differentiated the early stage of ovarian serous carcinoma(OSC) and advanced stage of OSC and try to find some miRNAs can predict the prognosis of OSC. Methods To identify a unique miRNA pattern associated with the progression of OSC at early and late stages, miRNA microarray was performed using Chinese tumor bank specimens of patients with OSC stage Ⅰ or stage Ⅲ in a retrospective analysis. 6 cases of stage ⅠOSC and 4 cases of stage Ⅲ OSC were included. The expression of miR-510, miR-509-5p, miR-508-3p, miR-483-5p were validated using real-time reverse transcription PCR in an external cohort of 16 cases of stage ⅠOSC and 35 cases of stage Ⅲ OSC samples. The expressions of these miRNAs were dichotomized to high and low expression, the relationship between the expression of these miRNA and clinicopathological characters and prognoses were analyzed. Results Of the 768 miRNAs analyzed in the microarray, 26 miRNAs were expressed differently including 6 miRNAs significantly up-regulated and 20 down-regulated, with at least a 2-fold difference, in OSC stage I compared to stage Ⅲ. The qRT-PCR results showed that miR-510, miR-509-5P, and miR-508-3p were significantly down-regulated and that miR-483-5p was up-regulated in stage Ⅲ OSC compared to stage ⅠOSC(P<0.05), which was consistented with the microarray results. The downregulation of miR-510 and miR-509 were significantly associated with poorer disease-specific survival(P<0.05). The 95% CI of overall survival timewas 72.455-96.668 for miR-510 high expression group and 32.356-57.019 for miR-510 low expression group. The 95% CI of overall survival time was 63.432-90.124 for miR-509-5p high expression group and 34.664-73.336 for miR-509-5p low expression group. Conclusions Our results suggested that miRNAs played an important role in the progression of OSC. The staging of OSC may be done depending on the miRNA expression profile. MiR-510 and miR-509 may be considered as novel candidate clinical biomarkers for predicting OSC outcome.更多还原