Song Ye, Zhu Haoran, Wei Junyang, Yin Shanxue
Department of Minimally Invasive Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, 150001, Harbin, China.
Xi 'an Jiaotong University Medical Center, Xi 'an, 710061, China.
Cancer Cell Int. 2025 Jun 21;25(1):226. doi: 10.1186/s12935-025-03855-2.
Disulfidptosis-related genes (DRGs) have emerged as key players in the prognosis of colon cancer(CC) and hold promise as potential therapeutic targets. This study systematically evaluates their prognostic significance and explores their potential for therapeutic intervention in colon adenocarcinoma.
Colon adenocarcinoma(COAD) samples were categorized based on DRG expression to analyze differences in the immune landscape across molecular subtypes. Variations between high-risk (HRG) and low-risk (LRG) groups and changes in cell population dynamics across different stages were examined. The expression patterns of Diaphanous-Related Formin 1 (DIAPH1) and NADH: Ubiquinone Oxidoreductase Subunit B10 (NDUFB10), key components of the prognostic model, were assessed during T cell development. The model was validated using external datasets, and single-cell analysis was performed to investigate spatial distribution differences in tumor-infiltrating cell populations.
DRGs were critical in modulating T cell differentiation in COAD. DIAPH1 and NDUFB10 showed significant fluctuations during T cell development, indicating their involvement in immune regulation. Single-cell analysis revealed distinct spatial distribution patterns between T cells and epithelial cells. The ProjecTILs algorithm identified a higher proportion of Th1 cells, while Graph Convolutional Network (GCN) analysis showed no significant differences in T cell subtype proportions across different phenotypes. In vitro experiments further demonstrated that the knockdown of DIAPH1 and NDUFB10 in T cells effectively inhibited tumor proliferation.
The DRG-based prognostic model demonstrated strong predictive power in COAD, highlighting the potential of DRGs as therapeutic targets. These findings provide a solid foundation for developing novel treatment strategies targeting disulfide ptosis pathways in CC.
二硫化物诱导细胞程序性坏死相关基因（DRGs）已成为结肠癌（CC）预后的关键因素，并有望成为潜在的治疗靶点。本研究系统评估了它们的预后意义，并探讨了其在结肠腺癌中进行治疗干预的潜力。
根据DRG表达对结肠腺癌（COAD）样本进行分类，以分析不同分子亚型的免疫格局差异。研究高危（HRG）组和低危（LRG）组之间的差异以及不同阶段细胞群体动态的变化。在T细胞发育过程中评估预后模型的关键组成部分——透明相关成膜蛋白1（DIAPH1）和NADH：泛醌氧化还原酶亚基B10（NDUFB10）的表达模式。使用外部数据集对该模型进行验证，并进行单细胞分析以研究肿瘤浸润细胞群体的空间分布差异。
DRGs在调节COAD中的T细胞分化中起关键作用。DIAPH1和NDUFB10在T细胞发育过程中表现出显著波动，表明它们参与免疫调节。单细胞分析揭示了T细胞和上皮细胞之间不同的空间分布模式。ProjecTILs算法识别出较高比例的Th1细胞，而图卷积网络（GCN）分析显示不同表型的T细胞亚型比例无显著差异。体外实验进一步证明，T细胞中DIAPH1和NDUFB10的敲低有效抑制了肿瘤增殖。
基于DRG的预后模型在COAD中显示出强大的预测能力，突出了DRGs作为治疗靶点的潜力。这些发现为开发针对CC中二硫化物诱导细胞程序性坏死途径的新型治疗策略提供了坚实基础。
