Researchers have identified a set of 3 differentially expressed genes (DEGs) that may play a role in the development of imatinib resistance in patients with a gastrointestinal stromal tumor (GIST), according to a study published in Frontiers in Genetics.

The genes FABP4, COL4A1, and RGS4 were discovered through bioinformatic analysis to be upregulated in an imatinib-resistant GIST cell line, compared to 2 imatinib-sensitive cell lines.

“It is suggested that these genes may play a potential role in the clinical diagnosis and treatment of imatinib resistance in GIST,” the study’s authors said. “The data in our study could provide useful information and direction for future study on GIST.”

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A comparison of DEGs between the imatinib-sensitive cell line GIST882 and the imatinib-resistant cell line GIST430 revealed a total of 897 genes. Of these genes, 431 were upregulated while 466 were downregulated.

Read more about GIST etiology.

Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the identified DEGs resulted in a list of the top 10 upregulated genes (NDN, FABP4, COL4A1, COLEC11, MEG3, EPHA3, EDN3, LMO3, RGS4, and CRISP2). GO analysis showed that the DEGs were involved in the regulation of a number of different functions including axonogenesis, neuron morphology, the development of vasculature, growth factor binding, and the extracellular matrix.

KEGG pathway analysis showed that DEGs were also possibly involved in a number of other diseases including human papillomavirus infection, Cushing syndrome, small-cell lung cancer, diabetic complications, amebiasis, and bladder cancer.

Using quantitative real-time PCR from 3 different cell lines after treatment with imatinib, the genes FABP4, COL4A1, and RGS4 were found to be significantly decreased in the imatinib-sensitive GIST882 and GIST-T1 cell lines compared to the imatinib-resistant GIST430 cell line.

FABP4 codes for the fatty acid-binding protein 4, which is mainly expressed in macrophages in adipocytes and has been associated with cardiovascular issues and a number of disorders including obesity and diabetes.

The COL4A1 gene controls a component of the extracellular matrix and has been linked to several cancers including human adenocarcinoma, breast cancer, and hepatocellular carcinoma.

Elevated levels of the regulators of G protein signaling 4 protein controlled by the RGS4 gene have also been linked to several human diseases, including cancers.


Cao L, Zheng K, Liu Y, et al. Identification of novel imatinib-resistant genes in gastrointestinal stromal tumors. Front Genet. Published online May 13, 2022. doi:10.3389/fgene.2022.878145