Molecular Landscape and Prognostic Value in the Post-Translational Ubiquitination, SUMOylation and Neddylation in Osteosarcoma: A Transcriptome Study.

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Post-translational modifications (PTMs) are crucial in cancer development.
• Limited research exists on PTM-related genes (PTMRGs) as prognostic biomarkers for specific cancers.
• Osteosarcoma (OS) pathogenesis and progression are influenced by PTMs.

Purpose of the Study:

• To investigate the role of PTM-related genes (PTMRGs) in osteosarcoma (OS).
• To develop a prognostic model for OS patient survival based on PTM patterns.
• To explore the association between PTMs, tumor microenvironment (TME), and immunotherapy response in OS.

Main Methods:

• Utilized gene expression data from TARGET and GEO repositories.
• Constructed a prognostic gene signature using LASSO Cox regression.
• Performed Gene Set Enrichment Analysis (GSEA) and Gene Ontology (GO) for pathway analysis.
• Validated gene function in OS cell lines using CCK-8, cell cycle, and immunofluorescence assays.

Main Results:

• Identified two distinct PTM patterns and gene clusters with significant prognostic implications.
• Observed significant differences in immune cell infiltration and function enrichment across PTM clusters.
• Demonstrated that low-risk patients benefit more from immunotherapy in external cohorts.
• Confirmed the expression and function of RAD21 in OS cells.

Conclusions:

• Established a novel link between PTMs and the immune infiltration landscape in osteosarcoma.
• Developed a new assessment protocol for precise treatment selection in advanced OS patients.
• Highlighted the potential of PTM-related genes as predictive biomarkers for OS prognosis and immunotherapy response.