CLEC3B as a Prognostic and Immunological Biomarker in Pan-Cancer: Multi-Omics Profiling and Validation in Pancreatic Cancer and Exosomes

Background: Despite the emergence of in vitro and in vivo experiments validating the connection between CLEC3B and various cancers, a comprehensive pan-cancer investigation remains elusive. In this study, we explored the potential roles of CLEC3B as a tumor suppressor and in immune function across multiple cancer types. Methods: We visualized outcomes derived from Gene Expression Omnibus (GEO) and diverse online databases. The relationship between tumor-infiltrating cells, gene set enrichment analysis (GSEA) and CLEC3B expression and was examined using R. Additionally, we explored the potential role of CLEC3B in tumor malignant behavior by using siRNA-mediated knockdown. Results: Our study identifies CLEC3B's low expression in majority of cancers compared with adjacent normal tissues. Reduced CLEC3B expression correlated with advanced clinical stages, inferior overall survival (OS) and DNA methylation levels. We observed significant positive associations between CLEC3B expression and infiltration levels of various immune cell subtypes. Furthermore, markers linked with immune checkpoints, immunomodulation and RNA modification exhibited a favorable correlation with CLEC3B expression. Intriguingly, silencing CLEC3B (si-CLEC3B) augmented the migratory capabilities of pancreatic adenocarcinoma (PAAD) cells. Additionally, CLEC3B expression was notably enriched in metastatic PAAD endothelial cells and extracellular vesicles, potentially implicating its involvement in tumor vascular function by way of extracellular vesicle. Conclusion: In conclusion, our initial pan-cancer analyses of CLEC3B provide insights into its associations with clinical prognosis, DNA methylation, immune cell infiltration, and tumor mutation burden, highlighting its potential as a tumor suppressor and mediator of immune infiltration in pan-cancer.