The role of the selenoproteome, which is the collection of all proteins containing selenium in an organism, in cancer development, growth and progression requires further investigation, due to the importance of selenium in both cancer and immune system function. Data about the selenoproteome, including its differential expression, single nucleotide variations, copy number variations, methylation, pathways and overall survival (OS) in five leading types of cancer are available from the GSCALite website. Subsequent to the analysis of these datasets, it was revealed that there was increased expression of GPX3 in stomach adenocarcinoma and lung squamous cell carcinoma, SELENOV in oesophageal carcinoma, GPX8 and GPX4 in colon adenocarcinoma, TXNRD1 and SEPHS1 in hepatocellular carcinoma and GPX8 in lung adenocarcinoma were associated with poor survival. Decreased gene expression of SELENOP was indicated in liver hepatocellular carcinoma and GPX3, and SELENOW, SELENOK, SELENBP1 and SECISBP2 in lung adenocarcinoma were associated with a poor prognosis. OS data suggested that hypermethylation of GPX4 in colon adenocarcinoma, GPX8 in lung squamous cell carcinoma, GPX1 in stomach adenocarcinoma and GPX3 in lung adenocarcinoma was associated with low survival, as is hypomethylation of GPX5 in lung adenocarcinoma. The selenoproteome is heterogeneous, especially in its effect on the OS of patients with cancer. The present study demonstrated that the roles of GPX4 in colon adenocarcinoma, SCLY and SELENOV in oesophageal carcinoma, SEPHS1 in liver hepatocellular carcinoma, SELENOK in lung cancer, as well as SELENOM and SELENOW in stomach adenocarcinoma requires further research. The present study may lead to the identification of novel biomarkers or potential therapeutic targets for use in the treatment of cancers, such as colon adenocarcinoma, oesophageal carcinoma, liver hepatocellular carcinoma, lung cancer and stomach adenocarcinoma.

Selenoprotein K (SELENOK) is an endoplasmic reticulum stress (ERS)-regulated protein required for the calcium (Ca²⁺) flux-mediated migration of T cells and neutrophils, and the migration and phagocytosis of macrophages and microglia. However, the effect of SELENOK on the regulation of the immune function of dendritic cells (DCs), including immature DCs (imDCs) and mature DCs (mDCs), is still unclear. In this study, imDCs prepared from SELENOK knockout mice were used to evaluate the effect of SELENOK on the migration and phagocytosis of imDCs. The results showed that ERS-induced downregulation of imDCs phenotypic markers led to a reduction in Ras homolog gene family member A (RhoA)-dependent migration and enhanced Ca²⁺/CD205-mediated phagocytosis. SELENOK deficiency-induced upregulation of selenoprotein S (SELENOS) attenuated ERS levels in imDCs. An increase in Ca²⁺ levels resulted in increased migration and decreased phagocytosis with or without ERS conditions. The migration was RhoA-dependent, and Ca²⁺ or CD205 was associated with regulating phagocytosis in imDCs. Our study found that SELENOK is required for imDC migration and phagocytosis.

Dendritic cells (DCs), the most potent antigen-presenting cells, play a central role in the initiation, regulation, and maintenance of the immune responses. Vascular endothelial growth factor (VEGF) is one of the important cytokines in the tumor microenvironment (TME) and can inhibit the differentiation and functional maturation of DCs. To elucidate the potential mechanisms of DC dysfunction induced by VEGF, the effects of VEGF on the biophysical characteristics and motility of human mature DCs (mDCs) were investigated. The results showed that VEGF had a negative influence on the biophysical properties, including electrophoretic mobility, osmotic fragility, viscoelasticity, and transmigration. Further cytoskeleton structure analysis by confocal microscope and gene expression profile analyses by gene microarray and real-time PCR indicated that the abnormal remodeling of F-actin cytoskeleton may be the main reason for the deterioration of biophysical properties, motility, and stimulatory capability of VEGF-treated mDCs. This is significant for understanding the biological behavior of DCs and the immune escape mechanism of tumors. Simultaneously, the therapeutic efficacies may be improved by blocking the signaling pathway of VEGF in an appropriate manner before the deployment of DC-based vaccinations against tumors.