Kai Nan,1,* Lei Zhang,2,* Yulong Peng,3 Jing Huang,3 Su Yin,3 Yujia Zou,4 Kaikai He,4 Ming Zhang5 

1Department of Joint Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, 710054, People’s Republic of China; 2Department of Pharmacy, Shaanxi Provincial Hospital of Chinese Medicine, Xi’an, Shaanxi, 710003, People’s Republic of China; 3Department of Orthopaedics, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710000, People’s Republic of China; 4Department of Rehabilitative Medicine, Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, 712046, People’s Republic of China; 5Department of General Practice, Honghui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, 710054, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Ming Zhang, Department of General Practice, Honghui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi Province, 710054, People’s Republic of China, Email zhangminghonghui@yeah.net

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.

Keywords: CLEC3B, pan-cancer, methylation, immune infiltration, tumor microenvironment