488O - Serum miRNA discriminates treatment-naive localized synovial sarcoma patients from those in follow-up after radical combined therapy

Abstract

Background: Synovial sarcoma (SySa) is an aggressive neoplasm that accounts for approximately 10% of all soft-tissue tumors. The levels of miRNAs in blood circulation was investigated in the past for SySa patients with array technology, however to date no exploratory next-generation sequencing (NGS) approach was used to evaluate blood circulating miRNA as response markers of SySa treatment. We present data coming from patients with locally advanced synovial sarcoma treated according to a uniform protocol of preoperative therapy (chemotherapy and radiotherapy). Methods: Serum samples of 28 SySa patients prior to preoperative therapy, following two courses of neoadjuvant chemotherapy (n = 23) and in follow-up after radical radiotherapy and surgery (n = 18) as well as the serum of healthy 30 donors were collected. 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. Comparisons were made between samples before treatment and those during treatment, in observation after treatment as well as healthy controls. Separate comparisons were also made for samples before and after surgical treatment. Results: Deep sequencing identified 1370 miRNAs. 47 miRNAs differentiated (adj. p- value <0.05) samples after treatment or in observation from those before chemotherapy and/or surgery. Out of these, two miRNAs were present in both comparisons and had good discriminative properties: hsa-miR-31-5p and hsa-miR-127-5p (Area Under the Curve - AUCs ranging from 0.75 to 0.87). In addition 49 miRNAs differentiated patients before treatment from healthy controls, 8 of which were also present in previous comparisons (hsa-miR-423-5p, hsa-miR-320a, hsa-miR-339-5p, hsa-miR-214-3p, hsa-miR-486-3p, hsa-miR-150-5p, hsa-miR-214-5p, hsa-miR-769-5p). However, none of these miRNAs reached AUCs above 0.8. Conclusions: Our NGS-based approach have identified blood circulating miRNAs with high to good discriminative properties to differentiate treatment-naive and SySa patients after treatment or in observation following the surgery. Further evaluation on an independent group of patients is warranted to confirm their value as a biomarker for the diagnosis of SySa recurrence or metastasis. Legal entity responsible for the study: Piotr Rutkowski Funding: National Science Center [2013/11/B/NZ5/03165 to PR] Disclosure: All authors have declared no conflicts of interest.