A Comprehensive Analysis of the Role of DSN1 in Pan-Cancer Prognosis and Immunotherapy.

Abstract

Background: Dosage Suppressor of NNF1 (DSN1) is a component of the MIS12 kinetochore complex crucial in the cell cycle process. Recent evidence indicates its close association with cancer progression. The study aims to further explore DSN1's role in cancer. Methods: Using public databases, we investigated the expression patterns of DSN1 in mRNA, protein, and single-cell sequencing data across cancer types. Prognostic associations were assessed through survival analysis, and gene mutation frequencies were compared between high and low DSN1 expression groups. Gene set enrichment analysis was conducted to identify relevant biological pathways. We also examined the correlation of DSN1 with DNA methylation, tumor mutation burden (TMB), microsatellite instability (MSI), immune infiltration, and immune-regulatory genes. Results: Our analysis revealed that DSN1 is consistently overexpressed in tumor cells and actively dividing cells compared to normal tissues. The overexpression of DSN1 showed a significant correlation with either poor or favorable prognosis, depending on the cancer type. Notably, cancers such as COAD, LUAD, and UCEC exhibited high mutation and amplification frequencies in the DSN1-high group. Gene set enrichment analysis identified cell cycle-related pathways as the most significantly associated with DSN1 expression. Furthermore, DSN1 expression was positively correlated with DNA methylation, TMB, and MSI in most cancers. DSN1 was also closely associated with tumor-infiltrating immune cells and immune-regulatory genes, as well as immune therapy response and drug sensitivity. Conclusion: Our findings highlight the importance of DSN1 in tumorigenesis, progression, and immune therapy across various cancer types. Further studies are needed to explore its specific applications in individual cancer types.