A bioinformatics and experimental approach identifies glycoprotein-based diagnostic and prognostic biomarkers for...

Colon adenocarcinoma (COAD) remains a leading cause of cancer-related mortality worldwide, partly due to the lack of robust biomarkers for early diagnosis and accurate prognosis. Glycoproteins play critical roles in tumorigenesis and may serve as promising sources of biomarkers. This study aimed to identify glycoprotein-related candidate diagnostic and prognostic biomarkers for COAD through integrated bioinformatics approaches and experimental validation. Gene expression profiles and clinical information of COAD patients were obtained from The Cancer Genome Atlas database (TCGA). The expression data for genes associated with glycoprotein were retrieved from the UniProt database. Furthermore, we assessed the mRNA expression levels of the glycoprotein FJX1 in COAD and rectal adenocarcinoma tissues through in situ hybridization (ISH) staining using tissue microarrays. A total of 228 glycoprotein-related differentially expressed genes (DEGs) were identified, enriched in the extracellular matrix organization and signaling pathways such as PI3K-Akt and cAMP. Protein-protein interaction (PPI) network analysis revealed 10 hub genes (LIFR, CNTFR, LIF, CSF2, IL1A, CSF3, F2, FGA, FGFR2, INHBA). Survival screening and multivariate Cox regression identified FJX1 as an independent prognostic factor for overall survival after adjusting for age and stage. FJX1 mRNA was significantly overexpressed in COAD tissues compared to normal (p < 0.001), and high FJX1 expression correlated with advanced T stage, M stage, and pathological stage. ISH confirmed elevated FJX1 mRNA in tumors. Immune infiltration analysis further revealed that high FJX1 expression was associated with increased infiltration of M0 macrophages and neutrophils, and decreased resting memory CD4⁺ T cells, suggesting a potential role in shaping the immunosuppressive tumor microenvironment. GSEA revealed significant enrichment of MAPK signaling in high-FJX1 tumors. In conclusion, this study identified 10 glycoprotein-related hub genes as candidate diagnostic biomarkers warranting further validation and established FJX1 as an independent prognostic biomarker for COAD. FJX1 overexpression is associated with tumor progression and may be linked to MAPK signaling as well as immune modulation. These findings provide a foundation for glycoprotein-based biomarker development in COAD.