Serum miR-518e-5p is a potential biomarker for secondary imatinib-resistant gastrointestinal stromal tumor

Abstract

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumor of the intestinal tract. Imatinib is used as first-line therapy for GIST patients; however, secondary imatinib resistance poses a significant clinical challenge. Here, we analyzed serum miRNA expression profiles to identify specific serum miRNAs that could be used as early diagnostic markers. Candidate miRNAs were validated using Taqman quantitative PCR with serum samples from secondary imatinibresistant GIST patients (n = 39), imatinib-sensitive GIST patients (n = 37), and healthy controls (n = 28). Serum miR- 518e-5p and miR-548e levels were higher in secondary imatinib-resistant GIST than imatinib-sensitive GIST patients or healthy controls (P less than 0.0001). However, ROC analysis indicated that only miR-518e-5p could distinguish imatinibresistant GIST. To discriminate imatinib-resistant from imatinib-sensitive GIST patients, the AUC for serum miR-518e-5p was 0.9938, with 99.8% sensitivity and 82.1% specificity. Serum miR-518e-5p could also discriminate imatinib-resistant GIST patients from healthy controls with 99.9% sensitivity and 97.4% specificity. These data indicate that serum miR-518e- 5p is a potentially promising non-invasive biomarker for early detection and diagnosis of secondary imatinib-resistant GIST.