基于功能组学数据识别卵巢癌风险microRNA

Identification of miRNA expression in ovarian cancer based on functional genomic data

目的通过生物信息学与免疫组化实验相结合的方法,探讨新的卵巢癌发病相关microRNA(miRNA)。方法选取2004年1月至2006年3月间哈尔滨医科大学附属第一医院及哈尔滨医科大学附属第三医院收治的70例上皮性卵巢癌手术病例石蜡包埋样本,采用SP免疫组化法进行检测,设阴性对照组及阳性对照组,阳性反应观察采用双盲法。以Gene Ontology为功能组学背景,度量不同基因之间的功能相似性得分,根据得分综合排序,寻找卵巢癌风险miRNA。应用该方法对2 588个miRNA进行优化排序,通过免疫组化实验方法对风险miRNA在卵巢癌中调控位点进行证实。结果优化后,卵巢癌相关miRNA如miR-200a/b/c排在前列,排序前10位miRNA中的大部分都在正常组织和卵巢癌组织中呈差异表达。miR-125a调控的人表皮生长因子-2(HER-2)呈高表达趋势。HER-2表达水平与临床分期,病理分级及存活时间显著相关,差异有统计学意义(P<0.05)。结论 miR-125a通过调控HER-2影响卵巢癌的临床病理特征,可成为新的卵巢癌相关风险因子。

Objective To find new microRNAs（miRNA） related to ovarian cancer through integration of bioinformatics and immunohistochemical methods. Methods Paraffin-embedded samples from 70 patients who underwent surgery for epithelial ovarian cancer were selected at The First Affiliated Hospital of Harbin Medical University and The Third Affiliated Hospital of Harbin Medical University from January 2004 to March 2006. Functional similarity score between genes were evaluated based on Gene Ontology and integrated sorting was performed according to the functional similarity score. A total of 2588 miRNAs achieved priority ordering by this method. The miRNA targeting sites in ovarian cancer were further tested by immunohistochemical method. Results After prioritization,several already known ovarian cancer related miRNAs such as miR-200a/b/c were ranked in top. Most top 10 miRNAs were differently expressed across normal and ovarian cancer samples. Human epidermal growth factor receptor 2（HER-2） regulated by miR-125 a were highly expressed. Conclusion By regulating HER-2,miR-125 a can impact the clinicopathological features of ovarian and further may be considered as new ovarian cancer related risk factors.