The Oncogenic and Prognostic Significance of NSUN5 in Pan-Cancer and Its Potential roles in Clear Renal Cell Carcinoma

Abstract Background: NSUN5, belonging to the NOL1/NOP2/SUN domain (NSUN) family, is implicated in RNA stabilization and widely expressed in different tumor types. Nevertheless, its precise role in pan-cancer, particularly its involvement in immunotherapy, remains poorly understood. Methods: The publicly available databases and the vitro experiments were used to investigate the roles of NSUN5 in human tumors. CellMiner database and Checkmate-025 cohort analyzed the sensitivity of NSUN5 with various drugs, particularly in PD-1 inhibitor. Subsequently, we constructed models to predict prognosis based on the expression of NSUN5 in kidney renal clear cell carcinoma (KIRC), glioma (GBM) and hepatocellular carcinoma (LIHC) cohorts. We further investigate the association between NSUN5 expression levels and immune cell infiltration. Gene Set Enrichment Analysis (GSEA) was used to identify the potential pathways with NSUN5 expression. Results: Differential analysis revealed that 18 types of tumors expressed NSUN5 to a greater extent than normal tissues. An easy-to use nomogram based on NSUN5 and several clinicopathological factors can excellently predict the prognosis of patients with GBM, KIRC, and LIHC. In addition, NSUN5 over-expression was positively correlated with exhausted CD8+ T cells and Tregs. Particularly, KIRC patients with heightened NSUN5 expression who underwent PD-1 inhibitor exhibited a poorer prognosis. In vitro results showed that NSUN5 down-expression promoted tumor cell senescence while hindered cell proliferation and migration. Conclusion: These findings inferred that NSUN5 acts as a prognostic factor to predict the OS in multiple types of tumors and implied the importance of developing novel immunotherapeutic strategies.