Circulating miR-26a as Potential Prognostic Biomarkers in Pediatric Rhabdomyosarcoma

Lucia Tombolan; Caterina Millino; Beniamina Pacchioni; Manuela Cattelan; Angelica Zin; Paolo Bonvini; Gianni Bisogno

doi:10.3389/fgene.2020.606274

Circulating miR-26a as Potential Prognostic Biomarkers in Pediatric Rhabdomyosarcoma

Front Genet. 2020 Dec 10:11:606274. doi: 10.3389/fgene.2020.606274. eCollection 2020.

Authors

Lucia Tombolan¹, Caterina Millino², Beniamina Pacchioni², Manuela Cattelan³, Angelica Zin¹, Paolo Bonvini¹, Gianni Bisogno^{1

4}

Affiliations

¹ Institute of Pediatric Research (IRP), Fondazione Città della Speranza, Padua, Italy.
² Functional Genomics Laboratory, Department of Biology, University of Padua, Padua, Italy.
³ Department of Statistical Sciences, University of Padua, Padua, Italy.
⁴ Department of Woman's and Children's Health, Hematology and Oncology Unit, University of Padua, Padua, Italy.

Abstract

Rhabdomyosarcoma (RMS) arises from myogenic precursors that fail to complete muscle differentiation and represents the most frequent soft tissue sarcoma in children. Two major histological subtypes are recognized: alveolar RMS, characterized by a more aggressive behavior and a greater proneness to metastasis, and embryonal RMS which accounts for the 80% of cases and carries a better prognosis. Despite the survival of patients with localized tumors has progressively improved, RMS remains a challenging disease especially for metastatic patients and in case of progressive or recurrent disease after front-line therapy. MicroRNAs, a class of small non-coding RNA, have emerged as crucial players in cancer development and progression, and their detection in plasma (circulating miRNAs) represents a promising minimally invasive approach that deserve to be exploited in clinical practice. We evaluated the utility of circulating miRNAs as diagnostic and prognostic biomarkers in children with RMS profiling miRNAs from plasma of a small cohort of RMS patients and healthy donors (HD) using a qPCR Cancer Panel. An assessment of hemolysis status of plasma using miR-451/miR-23a ratio was performed as pre-analytical analysis. Statistical analysis revealed that miRNAs expression pattern clearly distinguished RMS patients from HD (p < 0.05). Interestingly, plasma levels of muscle-specific miR-206 were found to be significantly increased in RMS patients compared to HD, whereas levels of three potential tumor-suppressor miRNAs, miR-26a and miR-30b/30c, were found lower. Reduced levels of circulating miR-26a and miR-30b/c were further measured in an independent larger cohort of patients (validation set) by digital droplet PCR. In particular, we evidenced that miR-26a absolute plasma levels were associated with fusion status and adverse outcome (p < 0.05). Taken together, these findings demonstrate the potential of circulating miRNA as diagnostic and prognostic biomarker in children affected by this malignancy and enforced the key role of miR-26a in pediatric rhabdomyosarcoma.

Keywords: circulating microRNAs; ddPCR; miR-26a; pediatric tumor; rhabdomyosarcoma.