整合分析基因表达与拷贝数变异识别癌症的驱动基因及调控子miRNAs

Integrative Analysis of Gene Expression with Copy Number Variation Identifies Driver Genes and Regulator-miRNAs in Cancers

目的:通过整合分析基因的表达与拷贝数变异(CNV)识别癌症的驱动基因及调控子mi RNAs。方法:通过整合基因表达与CNV数据,分别计算了乳腺癌、结肠癌、肺癌、肾癌、膀胱癌、头颈癌六种癌症中mi RNAs的调控得分,提出了一个识别驱动基因和显著调控子mi RNAs的方法。结果:本文研究发现,CNV区域上编码的基因相比于非CNV区域上编码的基因更倾向于受mi RNAs调控。但是,癌相关CNV区域上的基因相比正常CNV区域上的基因更少受mi RNAs调控。本研究识别出了EXOSC4、ZNF7、BOP1等原癌基因,以及mi R-488、mi R-27a、mi R-454等在多种癌症中都起调控作用的调控子mi RNAs。结论:本文的方法为癌症研究带来了新的启发,这些具有调控扩增基因过表达作用的mi RNAs的发现,有助于我们更进一步了解癌基因表达的复杂调控机制,进而推动癌症的诊断、治疗和预后。

Objective： By integrating analysis of gene expression and copy number variation to identify driver genes and regulator-miRNAs in cancers. Methods： The balancer score of miRNA in six cancer types including breast carcinoma, colon adenocarcinoma,head and neck squamous cell carcinoma, kidney renal clear cell carcinoma, lung adenocarcinoma and bladder urothelial carcinoma were computed by integrated gene expression and copy number variation data. A novel approach was developed to identify driver genes and significant regulator-miRNAs. Results： Our study indicated that compared with those in non-CNVs regions, genes in CNVs regions were more likely to be regulated by miRNA, but genes in cancer-related CNVs regions were less regulated by miRNA than genes in normal CNVs regions. We identified a set of oncogene such as EXOSC4, ZNF7, BOP1 and miRNAs which play a role as balancer in cancer cell such as miR-488, miR-27 a, miR-454. Conclusions： Our research provides a new approach to cancer study. Identifying these miRNAs help us further understand the complicated mechanism of regulation on gene expression, and improve the diagnosis, prognosis and therapy in cancer.