Abstract
The lack of useful biomarkers is a crucial problem for patients with soft tissue sarcomas (STSs). Emerging evidence has suggested that circulating microRNAs (miRNAs) in body fluids have novel impact as biomarkers for patients with malignant diseases, but their significance in synovial sarcoma (SS) patients remains unknown. Initial global miRNA screening using SS patient serum and SS cell culture media identified a signature of four upregulated miRNAs. Among these candidates, miR-92b-3p secretion from SS cells was confirmed, which was embedded within tumour-derived exosomes rather than argonaute-2. Animal experiments revealed a close correlation between serum miR-92b-3p levels and tumour dynamics. Clinical relevance was validated in two independent clinical cohorts, and we subsequently identified that serum miR-92b-3p levels were significantly higher in SS patients in comparison to that in healthy individuals. Moreover, serum miR-92b-3p was robust in discriminating patients with SS from the other STS patients and reflected tumour burden in SS patients. Overall, liquid biopsy using serum miR-92b-3p expression levels may represent a novel approach for monitoring tumour dynamics of SS.
Highlights
Synovial sarcoma (SS) is a high-grade soft tissue sarcoma (STS) that accounts for 10% to 20% of STSs in adolescents and in the young adult population[1,2]
Forty-nine serum miRNAs were significantly upregulated in SS patients compared with controls, and eight among these 49 miRNAs were markedly reduced at post-operative status compared to pre-operative status
MiRNA dysregulation in SS cells or tissue specimens has been reported by several groups (Supplementary Table S7)[13,14,15,16,17,18]
Summary
Synovial sarcoma (SS) is a high-grade soft tissue sarcoma (STS) that accounts for 10% to 20% of STSs in adolescents and in the young adult population[1,2]. Since the outcomes are far worse for SS patients who present with local recurrence or metastasis, the early diagnosis of tumour, recurrence, metastasis, and even drug response is crucial for better management This tumour is characterized by the SS18-SSX fusion gene, and the presence of this chromosomal translocation is clinically useful as a diagnostic marker. It does not reflect disease progression and is only evaluated using tumour specimens surgically resected[6]. While evidence on circulating miRNAs has been accumulated in various cancers, there has been little involving the soft tissue sarcomas, which to date lack useful circulating biomarkers. We investigated the expression profiles of serum cell-free miRNAs using blood samples from SS patients as well as in other STS patients, compared to controls, followed by the evaluation of biological and clinical significance using in vitro and in vivo experimental procedures and involving independent patient cohorts
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