(P 134) INTEGRATIVE MICRORNA PROFILING IN CHONDROSARCOMA: TOWARD BIOMARKER DISCOVERY AND PROGNOSTIC SIGNATURE DEVELOPMENT

Objective: Chondrosarcoma (ChSA) is an aggressive cartilaginous malignancy with poor response to conventional therapies and limited prognostic tools. MicroRNAs (miRNAs) are known regulators of gene expression in cancer, yet their role in ChSA remains poorly defined. This study aims to characterize global miRNA expression patterns in ChSA to uncover potential biomarkers and regulatory mechanisms linked to tumor progression.

Methods: Formalin-fixed paraffin-embedded (FFPE) tumor and adjacent normal tissues were collected from 40 ChSA patients. Total RNA was extracted, and small RNA sequencing was performed to profile miRNA expression. Differential expression analysis using DESeq2 identified significantly altered miRNAs (|log₂FC| > 1.5, p-adjusted < 0.05). Bioinformatic tools, including TargetScan and miRTarBase, were applied for target gene prediction and pathway enrichment analysis. Future plans include expanding the cohort to 60 cases, stratifying by tumor grade, and integrating clinical outcome data.

Results: Distinct miRNA expression patterns differentiated tumors from normal cartilage. Dysregulation was prominent in the miR-7a-345 and miR-7a-100-122 networks. miR-4488 was among the most upregulated (log₂FC > 5, p < 0.05). Over 50 miRNAs showed strong differential expression. Upregulated miRNAs included miR-100, miR-134, miR-140, miR-199, miR-214, miR-455, and miR-98, while miR-139, miR-142, miR-150, miR-183, miR-223, miR-486, and miR-744 were downregulated. Target gene analysis highlighted oncogenic pathways involving MYC, BCL2, NCOA3, and MTUS1.

Conclusion: This study provides the first comprehensive miRNA expression profile in ChSA, revealing dysregulated miRNA networks associated with tumor biology. These findings lay the groundwork for identifying clinically relevant miRNA biomarkers for diagnosis, prognosis, and therapeutic targeting in Chondrosarcoma.