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

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.

Detection of circulating tumor-derived material in peripheral blood of pediatric sarcoma patients: A systematic review

“…After the removal of 34 duplicates, 949 articles were screened of which 834 studies were deemed irrelevant based on the eligibility criteria. Of the 34 duplicates, 21 studies were included in this systematic review [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] . Full text screening of the remaining 115 articles resulted in 79 studies assessed eligible for qualitative synthesis and listed in Table 1 .…”

EZH2: A Critical Competing Endogenous RNA in Cancer Research - A Scoping Review

“…For instance, circulating levels of miR-26a-5p in plasma of patients with pediatric rhabdomyosarcoma are downregulated. Furthermore, patients with higher expression of miR-26a-5p have longer overall and progression free survival in this type of cancer (90). miR-26a-5p is also downregulated in breast cancer tissues.…”

Non-coding RNA in rhabdomyosarcoma progression and metastasis

“…Comparing circulating serum levels of known tumor suppressive miRNA in RMS patients to healthy donors, miR-26a and miR-30b/30c were found lower in RMS patients (59). Furthermore, low levels of circulating miR-26a significantly correlated with progressive disease but this requires further study to determine whether circulating miR-26a could act as a biomarker in RMS patients (59).…”

“…Their circulation and detection in body fluids is especially important in allowing their use in monitoring disease progression and treatment success. We mention, for example, how comparing serum levels of circulating miR-26a and miR-30b/30c distinguishes between RMS patients and healthy donors as these miRNA are detected at lower levels in RMS patients ( 59 ). This indicates that these miRNA have a potential role in patient diagnosis.…”