Title : Digital profiling of protein and microRNA in Rhabdomyosarcoma
Abstract:
Rhabdomyosarcoma exhibits a complex prognostic algorithm based on histologic, biologic and clinical parameters. In contrast to alveolar rhabdomyosarcoma, embryonal (ERMS) and spindle cell and sclerosing rhabdomyosarcoma (SRMS) histologic types exhibit more heterogenous molecular features and variable clinical behavior. The expression of signaling pathways and microRNA sets has not been previously studied in relation to prognosis and pathologic types of rhabdomyosarcoma. To identify relevant biomarkers using NanoString digital technology, we have studied 12 ERMS and SRMS cases with clinical information, categorized into adverse prognosis (n=5) and favorable prognosis groups (n=7) based on differences in patients’ overall survival. Formalin-fixed paraffin-embedded tumor tissue was subjected to digital spatial profiling and microRNA analysis. Digital spatial profiling revealed enrichment for PI3K/AKT, MAPK, and apoptosis signaling pathways with over-expression of several pathway members. Compared to the group with favorable prognosis, the adverse prognosis tumors had significantly increased expression of INPP4B (p<0.05), that was confirmed with traditional immunohistochemistry. Significant upregulation of miR-3144-3p, miR-612, miR-302d-3p, miR-421, miR-548y and miR-548ar-5p (p<0.05) was also noted in the unfavorable prognosis group. In conclusion, NanoString digital molecular profiling is a novel way of deciphering dysregulated signaling pathways and microRNA profiles from formalin-fixed paraffin embedded tumor tissue. Digital profiling may identify prognostic biomarkers in rhabdomyosarcoma.
