Researchers from China developed a new model to predict secondary imatinib-resistant gastrointestinal stromal tumors (GISTs). Bioinformatic mining results of the study “provide potential and promising targets for imatinib-resistant therapy,” they said in a study published in the Scandinavian Journal of Gastroenterology.

Imatinib is a drug that inhibits KIT signaling, which is involved in the pathogenesis of GIST. However, more than half of advanced or metastatic GIST cases become resistant to imatinib treatment within 2 years after starting treatment.

To understand the mechanism of how acquired imatinib-resistance develops in GIST, the team led by Yingjiang Ye from Peking University Peoplès Hospital, in Beijing, China, first analyzed the gene expression profile of GIST cases sensitive to imatinib and resistant to imatinib. This way, they identified 44 genes that were differentially expressed between the 2 types of GIST. These genes were mostly involved in DNA replication.


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The researchers then developed a model based on the expressed coefficients of 9 genes to identify a risk score to predict imatinib resistance and validated their model. Finally, they assessed the effect of immune, m6A, pyroptosis, and ferroptosis-related genes on imatinib resistance. 

They found that there were no significant differences in terms of tumor purity and immune score between samples that were imatinib sensitive or resistant suggesting that the immune status of GIST did not affect imatinib resistance.

They also found that some genes related to mRNA modification like m6A were more highly expressed while others were less highly expressed in imatinib-resistant GIST suggesting that they should be investigated further.

Similarly, genes related to pyroptosis and ferroptosis were differentially expressed between imatinib-resistant and imatinib-sensitive GIST, suggesting that they should also be studied further both to provide a rationale for imatinib resistance and as potential treatment targets.

Reference

Wang C, Shen Z, Jiang K, Gao Z, Ye Y. Establishment of the prediction model and biological mechanism exploration for secondary imatinib-resistant in gastrointestinal stromal tumor. Scand J Gastroenterol. 2022;18:1-10. doi:10.1080/00365521.2022.2087475