J Cancer 2020; 11(4):874-882. doi:10.7150/jca.34723

Research Paper

Signatures of circulating microRNA in four sarcoma subtypes

Hanna Kosela-Paterczyk1*, Agnieszka Paziewska2,3*, Maria Kulecka2,3, Aneta Balabas3, Anna Kluska3, Michalina Dabrowska3, Magdalena Piatkowska3, Natalia Zeber-Lubecka2, Filip Ambrozkiewicz3, Jakub Karczmarski3, Michal Mikula3, Piotr Rutkowski1✉, Jerzy Ostrowski2,3✉

1. Department of Soft Tissue, Bone Sarcoma and Melanoma, Maria Sklodowska-Curie Institute - Oncology Centre, Warsaw, Poland
2. Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, Warsaw, Poland
3. Department of Genetics, Maria Sklodowska-Curie Institute - Oncology Centre; 02-781 Warsaw, Poland
*Equal contribution

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Kosela-Paterczyk H, Paziewska A, Kulecka M, Balabas A, Kluska A, Dabrowska M, Piatkowska M, Zeber-Lubecka N, Ambrozkiewicz F, Karczmarski J, Mikula M, Rutkowski P, Ostrowski J. Signatures of circulating microRNA in four sarcoma subtypes. J Cancer 2020; 11(4):874-882. doi:10.7150/jca.34723. Available from http://www.jcancer.org/v11p0874.htm

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Background: Sarcomas are rare malignant tumors of mesenchymal origin. The discovery of circulating biomarkers with high diagnostic value could supplement diagnosis of this heterogenous group of tumors. The aim of this study was to identify the profiles of circulating miRNA (c-miRNAs) in four groups of common bone and soft tissue sarcomas.

Methods: At the time of diagnosis, blood samples were collected from 86 patients: 36 with locally advanced/unresectable/metastatic gastrointestinal stromal tumor (GIST) who received first-line treatment with imatinib; 16 with locally advanced osteosarcoma (OS); 26 with locally advanced synovial sarcoma (SS); and eight with locally advanced Ewing sarcoma (ES). In addition, samples were collected from 30 healthy controls. C-miRNAs were isolated using a miRCURY RNA Isolation Kit, followed by preparation of cDNA libraries and sequencing on the Ion Proton platform.

Results: Pair-wise comparisons identified 156 unique c-miRNAs (adjusted P-value < 0.05) showing significant dysregulation between controls and patients; of these, 24, 36, 42, and 99 differentiated controls from pretherapeutic OS, SS, ES, and GIST, respectively. Ten c-miRNAs were commonly altered in at least three sarcoma types. Receiver operating characteristic curves and area under the curve (ROC-AUC) analyses revealed that a four-miRNA diagnostic classifier was able to differentiate controls from ES, GIST, OS, and SS, with AUC-ROC values of 1, 0.97, 0.95, and 0.94, respectively.

Conclusions: Aberrant miRNA expression signatures were identified in serum from patients with four different sarcoma subtypes. Differences in miRNA expression profiles between sarcoma patients and healthy volunteers suggest that miRNAs may play a role in sarcoma development.

Keywords: miRNA, sarcoma, diagnosis, next generation sequencing