Wen Liang, Ma Yongli, Li Jinghui, Chen Dengzhuo, Huang Chengzhi, Wang Ping, Wen Suqi, Wen Gexin, Guo Jizhen, Zhang Guosheng, Wang Junjiang, Yao Xueqing
Gannan Medical University, Ganzhou, China.
Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital, Ganzhou, China.
Discov Oncol. 2025 Mar 18;16(1):354. doi: 10.1007/s12672-025-02142-w.
Disulfidptosis is a unique type of programmed cell death that is distinct from previously known forms of cell death, such as pyroptosis, apoptosis, and necroptosis. Researchers have studied the significance of many forms of cell death in various diseases, particularly malignant tumors, in great detail in recent years. Therefore, how disulfidptosis affects colon cancer and how it functions in the immune system are unknown.
Disulfidptosis-related gene (DRG) expression information was obtained from the TCGA-COAD cohort. Patients were categorized into two DRG groups using consensus cluster analysis, and the disulfidptosis-related differentially expressed genes (DRDEGs) were subsequently identified by differential analysis of the two clusters. Univariate Cox regression analysis of the DRDEGs was used to identify prognosis-related DEGs (PRDEGs). The screened PRDEGs were then subjected to LASSO-Cox regression analysis to determine the prognostic model on the basis of ten genes. Immunohistochemistry was used to verify the expression and prognostic value of marker genes.
In the two DRG clusters, the characteristics of the tumor microenvironment (TME) significantly differed by the TME scores and infiltration levels of 23 human immune cell subpopulations. Prognostically meaningful risk scores were found, with a greater chance of mortality (p = 4.4e-7) for patients in the high-risk category. Furthermore, notable differences in TME scores, immune cell infiltration, and immune checkpoint expression were detected among the risk categories. The ROC curves revealed that the nomogram's 1-, 2-, and 3-year AUCs were 0.75, 0.76, and 0.77, respectively, demonstrating the superior predictive capacity of the nomogram. Immunohistochemistry revealed that patients with high FABP4 and low ADAM8 and FSTL3 expressions had a better prognosis.
The prognostic features based on 10 PRDEGs performed well in predicting survival, TME status, and response to immunity in COAD patients, helping provide personalized immunotherapy strategies for patients.
二硫化物诱导的细胞焦亡是一种独特的程序性细胞死亡类型，与之前已知的细胞死亡形式，如细胞炎性坏死、凋亡和坏死性凋亡不同。近年来，研究人员对多种细胞死亡形式在各种疾病，特别是恶性肿瘤中的意义进行了深入研究。因此，二硫化物诱导的细胞焦亡如何影响结肠癌及其在免疫系统中的作用尚不清楚。
从TCGA-COAD队列中获取二硫化物诱导的细胞焦亡相关基因（DRG）表达信息。使用一致性聚类分析将患者分为两个DRG组，随后通过对两个聚类的差异分析确定二硫化物诱导的细胞焦亡相关差异表达基因（DRDEG）。对DRDEG进行单变量Cox回归分析以鉴定预后相关差异基因（PRDEG）。然后对筛选出的PRDEG进行LASSO-Cox回归分析，以确定基于10个基因的预后模型。采用免疫组织化学法验证标记基因的表达及预后价值。
在两个DRG聚类中，肿瘤微环境（TME）的特征在23种人类免疫细胞亚群的TME评分和浸润水平上存在显著差异。发现了具有预后意义的风险评分，高危组患者的死亡几率更高（p = 4.4e-7）。此外，在不同风险类别中检测到TME评分、免疫细胞浸润和免疫检查点表达存在显著差异。ROC曲线显示，列线图的1年、2年和3年AUC分别为0.75、0.76和0.77，表明列线图具有卓越的预测能力。免疫组织化学显示，FABP4高表达且ADAM8和FSTL3低表达的患者预后较好。
基于10个PRDEG的预后特征在预测COAD患者的生存、TME状态和免疫反应方面表现良好，有助于为患者提供个性化的免疫治疗策略。
