MicroRNA expression profile predicts prognosis of pediatric
adrenocortical tumors
Abstract
Pediatric adrenocortical tumors (ACT) are rare aggressive neoplasms with
heterogeneous prognosis. Despite extensive efforts, identifying reliable
prognostic factors for pediatric patients with ACT remains a challenge.
MicroRNA (miRNA) signatures have been associated with cancer diagnosis,
treatment response, and prognosis of several types of cancer. However,
the role of miRNAs has been poorly explored in pediatric ACT. In this
study, we performed miRNA microarray profiling on a cohort of 37
pediatric ACT and nine non-neoplastic adrenal (NNA) samples and
evaluated the prognostic significance of abnormally expressed miRNAs
using Kaplan-Meier plots, log-rank test and Cox regression analysis. We
identified a total of 98 abnormally expressed miRNAs, which expression
profile discriminated ACT from NNAs. Among the 98 deregulated miRNAs, 17
presented significant associations with patients’ survival. In addition,
higher expression levels of hsa-miR-630, -139-3p, -125a-3p, -574-5p,
-596, -564, -1321, and -423-5p and lower expression levels of
hsa-miR-377-3p, -126-3p, -410, -136-3p, -29b-3p, -29a-3p, -337-5p,
-143-3p, and 140-5p were significantly associated with poor prognosis,
tumor relapse, and/or death. Importantly, the expression profile of
these 17 miRNAs stratified patients into two groups of ACTs with
different clinical outcomes. Although some individual miRNAs exhibit
potential prognostic values in ACTs, only the 17 miRNA-based expression
clustering was considered an independent prognostic factor for five-year
event-free survival (EFS) compared to other clinicopathological
features. In conclusion, our study reports for the first time
associations between miRNA profiles and childhood ACT prognosis,
providing evidence that miRNAs could be useful biomarkers to
discriminate patients with favorable and unfavorable clinical outcomes.