Prognostic prediction and expression validation of NSD3 in pan-cancer analyses

Background: Nuclear receptor binding SET domain protein-3 (NSD3) is a histone lysine methyltransferase and a crucial regulator of carcinogenesis in several cancers. We aimed to investigate the prognostic value and potential function of NSD3 in 33 types of human cancer. Methods: The data were obtained from The Cancer Genome Atlas. Kaplan-Meier analysis, CIBERSORT, gene set enrichment analysis, and gene set variation analysis were performed. The expression of NSD3 was measured using quantitative real-time polymerase chain reaction and western blot. Results: The expression of NSD3 was altered in pan-cancer samples. Patients with higher levels of NDS3 generally had shorter overall survival and disease-specific survival. Levels of NSD3 were positively correlated with DNA copy number variation (CNV) in pan-cancer. NSD3 expression was also associated with tumor mutation burden and microsatellite instability. The levels of immune-cell infiltration differed significantly between high and low NSD3 expression. NSD3 negatively correlated with levels of CD8+ T cells. Functional enrichment analysis showed that while NSD3 expression was positively associated with several immune cell-related and histone methylation-related pathways, it was negatively correlated with cell metabolism-related, drug transport-related, and drug metabolism-related pathways. NSD3 levels in the cell lines tested were significantly different. In U251 and NCI-H23 cells, silencing NSD3 inhibited cell proliferation and promoted apoptosis. Conclusions: NSD3 expression was changed in pan-cancer samples that was also verified in cell lines. NSD3 was associated with CNV and immune-cell infiltration. A poor prognosis was predicted in patients with high expression of NSD3. NSD3 might hence be a potential marker for predicting tumor prognosis.