1514P - Serum miRNA abundances discriminate imatinib-naive patients with advanced gastrointestinal stromal tumors (GIST) from those in remission on Imatinib therapy

Abstract

Background: Deregulation of microRNAs (miRNAs) expression is observed virtually in all major types of neoplasm and miRNAs level in blood circulation are investigated as a potential diagnostics or prognostics biomarkers for neoplastic disorders. Gastrointestinal stromal tumors (GISTs) is the most common sarcoma of the gastrointestinal tract and to date performed studies on GISTs have provided mounting evidence on altered miRNA association with clinical, pathological features and Imatinib resistance in GIST. However, the utility of circulating miRNA as response markers of GIST progression and for Imatinib treatment have not been evaluated Methods: 36 metastatic or unresectable CD-117-positive GIST patients, were enrolled and serum sample was collected prior to Imatinib treatment. All patients responded initially to imatinib therapy. In 12 patients an additional serum sample was collected following targeted treatment at the time of remission. Control group comprised 30 healthy individuals. MiRNAs were isolated from serum with MirVANA miRNA Isolation Kit and then analyzed using deep sequencing on Ion Torrent PGM. Reads were mapped to miRBase miRNA collection with miRDeep2. Differential expression was evaluated with edgeR. Results: Deep sequencing identified 1284 miRNAs. The pair-wise comparison between Imatinib treated and Imatinib-naive GIST samples uncovered 22 miRNAs with differential expression (adjusted p value <0.05) of which 10 (miR-142-5p, let-7d-3p, miR-30e-5p, miR-194-5p, miR-223-5p, miR-223-3p, miR-125a-5p, miR-199b-5p, miR-24-2-5p, miR-641) yielded AUCs (areas under Receiver Operating Characteristic curves) ranging 0.81 and 0.9, thus having a high discriminative properties. A comparison of imatinib-naive GIST and control healthy samples revealed 99 differentially expressed miRNAs (adjusted p value <0.05) of which four (miR-582-5p, miR-150-5p, miR-450b-5p, miR-450a-5p) reached AUCs with high discriminatory power ranging 0.81-0.84. Conclusions: Circulating miRNA abundances can distinguish GIST patients from those in remission following Imatinib therapy as well as from the healthy controls. However, further studies evaluating the potential of designated microRNAs as response markers for treatment or as predictive markers of GIST are warranted. Legal entity responsible for the study: Piotr Rutkowski Funding: the grant from National Science Center [2013/11/B/NZ5/03165 to PR Disclosure: All authors have declared no conflicts of interest.