Department of Colorectal Surgery, the First Affiliated Hospital of Harbin Medical University, the First Affiliated Hospital of Harbin Medical University, Harbin, China.
Respiratory Medicine, Infectious Disease Hospital of Heilongjiang Province, Infectious Disease Hospital of Heilongjiang Province, Harbin, China.
Neoplasma. 2018 Sep 19;65(5):683-692. doi: 10.4149/neo_2018_170906N575. Epub 2018 Sep 4.
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. Imatinib mesylate was considered to be a breakthrough drug in clinical treatment of GIST, but GIST patients showed resistance against it. We aimed to identify critical microRNAs (miRNAs) related to imatinib resistance in imatinib-treated GIST patients. Microarray datasets under the accession number of GSE63159 and GSE45901 were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed miRNAs (DEMs) that are related to imatinib resistance were identified. GO function and KEGG pathway enrichment analyses were performed, and lncRNA-miRNA-target gene regulatory networks were constructed. Finally, the critical miRNAs and their target genes that are related to imatinib resistance or sensitivity were identified. In total, 20 DEMs in the GSE63159 dataset (7 significantly up-regulated and 13 down-regulated) and 23 DEMs in the GSE45901 dataset (8 up-regulated and 15 down-regulated) were identified. In lncRNA-miRNA-target gene regulatory networks, five critical miRNAs and 109 target genes were identified. GO function and KEGG pathway enrichment analysis showed that the target genes of DEMs were mainly involved in several signaling pathways, such as focal adhesion and the GnRH signaling pathway. Among the five miRNAs, the overexpression of hsa-miR-28-5p and hsa-miR-125a-5p had significant correlation to imatinib resistance or imatinib sensitivity in GIST patients. Hsa-miR-28-5p and hsa-miR-125a-5p may be involved in the development and progression of GIST, and they may be able to serve as prognostic markers for imatinib-response in GIST patients.
胃肠道间质瘤（GISTs）是胃肠道最常见的间叶性肿瘤。甲磺酸伊马替尼被认为是 GIST 临床治疗的突破性药物，但 GIST 患者对此表现出耐药性。本研究旨在鉴定与伊马替尼耐药相关的关键微小 RNA（miRNA）。从基因表达综合数据库（GEO）下载了注册号为 GSE63159 和 GSE45901 的微阵列数据集。鉴定与伊马替尼耐药相关的差异表达 miRNA（DEM）。进行了 GO 功能和 KEGG 通路富集分析，并构建了 lncRNA-miRNA-靶基因调控网络。最后，鉴定了与伊马替尼耐药或敏感性相关的关键 miRNA 及其靶基因。在 GSE63159 数据集中共鉴定出 20 个 DEM（7 个显著上调和 13 个下调），在 GSE45901 数据集中共鉴定出 23 个 DEM（8 个上调和 15 个下调）。在 lncRNA-miRNA-靶基因调控网络中，鉴定出 5 个关键 miRNA 和 109 个靶基因。GO 功能和 KEGG 通路富集分析显示，DEM 的靶基因主要参与了几个信号通路，如焦点黏附和 GnRH 信号通路。在这 5 个 miRNA 中，hsa-miR-28-5p 和 hsa-miR-125a-5p 的过表达与 GIST 患者对伊马替尼的耐药或敏感性具有显著相关性。hsa-miR-28-5p 和 hsa-miR-125a-5p 可能参与 GIST 的发生和发展，它们可能作为 GIST 患者对伊马替尼反应的预后标志物。
