Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
Int J Cancer. 2010 Apr 1;126(7):1640-50. doi: 10.1002/ijc.24897.
MicroRNAs are known to regulate gene expression. Although unique microRNA expression profiles have been reported in several tumors, little is known about microRNA expression profiles in GISTs. To evaluate the relationship between microRNA expression and clinicopathologic findings of GISTs, we analyzed the microRNA expression profiles of GISTs. We used fresh frozen tissues from 20 GISTs and analyzed KIT and PDGFRA mutations and chromosomal loss status. MicroRNA expression was analyzed using a microRNA chip containing 470 microRNAs. Using unsupervised hierarchical clustering analysis, we found four distinct microRNA expression patterns in our 20 GISTs. Six GISTs that did not have 14q loss formed a separate cluster. In the 14 GISTs with 14q loss, 5 small bowel GISTs formed a separate cluster and the remaining 9 GISTs could be divided into two groups according to frequent chromosomal losses and tumor risk. We found 73 microRNAs that were significantly down-regulated in the GISTs with 14q loss; 38 of these microRNAs are encoded on 14q. We also found many microRNAs that were down-regulated in small bowel and high-risk group GISTs. Most of the microRNAs down-regulated in the high-risk group and small bowel GISTs are known to be involved in tumor progression, specifically by stimulating mitogen-activated protein kinase (MAPK) and the cell cycle. The microRNA expression patterns of GISTs are closely related to the status of 14q loss, anatomic site, and tumor risk. These findings suggest that microRNA expression patterns can differentiate several subsets of GISTs.
MicroRNAs 已知可以调节基因表达。虽然已经在几种肿瘤中报道了独特的 microRNA 表达谱，但对 GISTs 的 microRNA 表达谱知之甚少。为了评估 microRNA 表达与 GISTs 的临床病理发现之间的关系，我们分析了 GISTs 的 microRNA 表达谱。我们使用来自 20 个 GISTs 的新鲜冷冻组织，分析了 KIT 和 PDGFRA 突变以及染色体缺失状态。使用包含 470 个 microRNAs 的 microRNA 芯片分析 microRNA 表达。通过非监督层次聚类分析，我们在 20 个 GISTs 中发现了四种不同的 microRNA 表达模式。没有 14q 缺失的 6 个 GISTs形成了一个单独的簇。在 14q 缺失的 14 个 GISTs中，5 个小肠 GISTs形成了一个单独的簇，其余 9 个 GISTs可以根据频繁的染色体缺失和肿瘤风险分为两组。我们发现 73 个 microRNAs 在 14q 缺失的 GISTs 中显著下调；其中 38 个 microRNAs 编码在 14q 上。我们还发现许多 microRNAs在小肠和高风险组 GISTs 中下调。在高风险组和小肠 GISTs 中下调的大多数 microRNAs 已知参与肿瘤进展，特别是通过刺激丝裂原活化蛋白激酶（MAPK）和细胞周期。GISTs 的 microRNA 表达模式与 14q 缺失、解剖部位和肿瘤风险密切相关。这些发现表明 microRNA 表达模式可以区分 GISTs 的几个亚群。
