Integrative Multi-Omics Profiling of Rhabdomyosarcoma Subtypes Reveals Distinct Molecular Pathways and Biomarker...

Area of Science:

• Oncology
• Biochemistry
• Pediatric Medicine

Background:

• Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma.
• RMS has two main subtypes: embryonal (ERMS) and alveolar (ARMS), with differing clinical outcomes.
• Molecular distinctions between ERMS and ARMS are not fully understood.

Purpose of the Study:

• To characterize the molecular differences between ERMS and ARMS using plasma proteomics and metabolomics.
• To identify subtype-specific molecular signatures, pathways, and potential biomarkers in pediatric RMS.
• To correlate molecular findings with clinical parameters.

Main Methods:

• Untargeted plasma proteomics and metabolomics profiling in children with ERMS, ARMS, and healthy controls.
• Differential expression analysis, functional enrichment (GO, KEGG, RaMP-DB), and co-expression network analysis (WGCNA/WMCNA).
• Multi-omics integration using DIABLO and MOFA for subtype discrimination.

Main Results:

• ARMS showed elevated oncogenic/stemness proteins and metabolites related to lipid and polyamine metabolism.
• ERMS was enriched in immune/myogenic proteins and metabolites linked to glutamate/glycine metabolism and redox homeostasis.
• Subtype-specific pathway activation (PI3K-Akt/Hippo in ARMS; immune/coagulation in ERMS) and associations with clinical parameters were observed.

Conclusions:

• Distinct molecular signatures differentiate ERMS and ARMS, aligning with clinical observations.
• Novel subtype-specific molecular programs and coordinated protein-metabolite modules were uncovered.
• Findings propose candidate biomarkers and pathways for precision diagnostics and therapeutics in pediatric sarcomas.