Identification of critical microRNAs in gastrointestinal stromal tumor patients treated with Imatinib

Zhenan Zhang, Nan-Yang Jiang, Ruo-Yu Guan, Yue-Kun Zhu, Feng-Qi Jiang,  Daxun Piao

Abstract:

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.