Enfield Katey S S, Stewart Greg L, Pikor Larissa A, Alvarez Carlos E, Lam Stephen, Lam Wan L, Chari Raj
British Columbia Cancer Research Centre, Vancouver, BC, Canada.
J Biomed Biotechnol. 2011;2011:474632. doi: 10.1155/2011/474632. Epub 2011 Mar 31.
Chemotherapy resistance is a key contributor to the dismal prognoses for lung cancer patients. While the majority of studies have focused on sequence mutations and expression changes in protein-coding genes, recent reports have suggested that microRNA (miRNA) expression changes also play an influential role in chemotherapy response. However, the role of genetic alterations at miRNA loci in the context of chemotherapy response has yet to be investigated. In this study, we demonstrate the application of an integrative, multidimensional approach in order to identify miRNAs that are associated with chemotherapeutic resistance and sensitivity utilizing publicly available drug response, miRNA loci copy number, miRNA expression, and mRNA expression data from independent resources. By instigating a logical stepwise strategy, we have identified specific miRNAs that are associated with resistance to several chemotherapeutic agents and provide a proof of principle demonstration of how these various databases may be exploited to derive relevant pharmacogenomic results.
化疗耐药是肺癌患者预后不佳的关键因素。虽然大多数研究集中在蛋白质编码基因的序列突变和表达变化上，但最近的报告表明，微小RNA（miRNA）表达变化在化疗反应中也起着重要作用。然而，miRNA基因座的基因改变在化疗反应中的作用尚未得到研究。在本研究中，我们展示了一种综合、多维方法的应用，以便利用来自独立资源的公开可用的药物反应、miRNA基因座拷贝数、miRNA表达和mRNA表达数据，识别与化疗耐药和敏感性相关的miRNA。通过采用合理的逐步策略，我们确定了与对几种化疗药物耐药相关的特定miRNA，并提供了一个原理证明，展示了如何利用这些不同的数据库得出相关的药物基因组学结果。
