Clinical utility of OGN in pan-cancer: diagnostic biomarker and immune microenvironment regulator

Osteoglycin (OGN), an extracellular matrix protein, has emerging but poorly characterized roles in cancer. This study presents the first pan-cancer investigation of OGN's expression patterns, clinical significance, immune interactions, and functional mechanisms.

Multi-omics data from Genotype Tissue Expression (GTEx), Cancer Cell Line Encyclopedia (CCLE), The Cancer Genome Atlas (TCGA), and Human Protein Atlas (HPA) databases were integrated. Differential expression was analyzed in normal tissues and tumor samples. Diagnostic utility was evaluated using area under the curve (AUC) of receiver operating characteristic (ROC) curve. Prognostic value was assessed via Kaplan-Meier [overall survival (OS); disease-specific survival (DSS); disease free interval (DFI); progression-free interval (PFI)] and Cox regression analyses. Immune microenvironment correlations were quantified using ESTIMATE, CIBERSORT, and gene set enrichment. Functional pathways were explored through gene set enrichment analysis (GSEA) and correlation with hallmark cancer signatures.

OGN was broadly expressed in normal tissues (brain, liver, kidney) but significantly downregulated in most tumor types (P<0.05, TCGA; validated at protein level, HPA). OGN demonstrated high diagnostic accuracy in pan-cancer (AUC: 0.703-0.990), achieving near-perfect performance in colon adenocarcinoma (COAD) (AUC: 0.966) and thyroid cancer (THCA) (AUC: 0.920). High OGN expression correlated with improved survival outcomes in thymoma (THYM) (OS/DSS) and cholangiocarcinoma (CHOL) (PFI/DFI), but worse prognosis in lung adenocarcinoma​/liver hepatocellular carcinoma​ (LUAD/LIHC), indicating cancer-type specificity. OGN expression strongly associated with immune cell infiltration (macrophages, natural killer cells, T cells), chemokine signaling, programmed death-ligand 1 (PD-L1) levels, microsatellite instability (MSI), and tumor mutation burden (TMB). GSEA revealed enrichment of OGN-linked genes in epithelial-mesenchymal transition (EMT), angiogenesis, JAK-STAT, and PI3K pathways across cancers.

Our pan-cancer analysis highlights OGN as a context-dependent regulator linking extracellular matrix (ECM) remodeling with immune and angiogenic signaling. Its pan-cancer dysregulation, diagnostic/prognostic value, and crosstalk with immune evasion mechanisms nominate OGN as a promising multi-functional biomarker and therapeutic target.