Xu Donggang, Zhang Yue, Shen Maoqia, Cao Xiaolong
Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, Guangdong, China.
Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, Guangdong, China.
J Cancer. 2025 Apr 21;16(8):2449-2465. doi: 10.7150/jca.111585. eCollection 2025.
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. 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. 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. 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.
NNF1剂量抑制因子（DSN1）是MIS12动粒复合体的一个组成部分，在细胞周期进程中至关重要。最近的证据表明它与癌症进展密切相关。本研究旨在进一步探索DSN1在癌症中的作用。我们利用公共数据库，研究了DSN1在多种癌症类型的mRNA、蛋白质和单细胞测序数据中的表达模式。通过生存分析评估预后关联，并比较DSN1高表达组和低表达组之间的基因突变频率。进行基因集富集分析以确定相关的生物学途径。我们还研究了DSN1与DNA甲基化、肿瘤突变负荷（TMB）、微卫星不稳定性（MSI）、免疫浸润和免疫调节基因的相关性。我们的分析表明，与正常组织相比，DSN1在肿瘤细胞和活跃分裂细胞中持续过表达。DSN1的过表达根据癌症类型显示出与不良或良好预后显著相关。值得注意的是，在DSN1高表达组中，如结肠癌（COAD）、肺腺癌（LUAD）和子宫内膜癌（UCEC）等癌症表现出高突变和扩增频率。基因集富集分析确定细胞周期相关途径与DSN1表达最显著相关。此外，在大多数癌症中，DSN1表达与DNA甲基化、TMB和MSI呈正相关。DSN1还与肿瘤浸润免疫细胞和免疫调节基因以及免疫治疗反应和药物敏感性密切相关。我们的研究结果突出了DSN1在各种癌症类型的肿瘤发生、进展和免疫治疗中的重要性。需要进一步研究以探索其在个体癌症类型中的具体应用。
