Title : MicroRNA expression in pediatric sarcoma
Abstract:
MicroRNAs are small non-coding RNA molecules that play a significant role in many physiological processes in the body, including posttranscriptional regulation of gene expression. Their expression in cancer cells can become dysregulated to influence the devlopment of cancer. Although they have been extensively studied in adult cancers, their roles in pediatric sarcomas remain poorly defined. In order to define the microRNA profile associated with three common pediatric sarcomas, we used multiple tissue samples from different sources to detect microRNA differential expression in 26 Ewing’s sarcoma, 50 rhabdomyosarcoma, and 32 osteosarcoma cases. We have used the NanoString multiplex nCounter platform to identify the expression of 827 human miRNAs and confirmed our findings with microRNA in situ hybridization (miRNA-ISH) of specific probes on tissue sections. The differential expression analysis of nCounter data identified 23 miRNAs enriched in RMS, 33 in EWS, and 45 in OS. miR-206 was most strongly associated with RMS and demonstrated the highest sensitivity and specificity in distinguishing RMS from EWS and OS; this finding was also confirmed by miRNA-ISH. A combined signature of differentially expressed miRNAs reliably separated alveolar from embryonal RMS. The expression of miR-9-5p in EWS and miR-140-5p in OS discriminated among the different tumors and correlated with adverse patient outcome. The NanoString nCounter profiling method exhibited higher sensitivity in detecting profiles and differential expression of microRNAs compared with microRNAscope which identified the in situ hybridization of specific microRNA molecules. MicroRNA expression correlated with adverse patient outcome. Our findings demonstrate that distinct miRNA profiles can differentiate pediatric sarcoma types and provide clinically relevant insights into potential diagnostic and prognostic applications.
