Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, China.
Aging (Albany NY). 2023 Dec 27;15(24):15434-15450. doi: 10.18632/aging.205365.
Disulfidptosis is a novel type of cell death mediated by SLC7A11-induced disulfide stress. Gastric cancer (GC) is a common malignant gastrointestinal tumor. Existing evidence shows that SLC7A11 can regulate cell death and improve the progression of GC, suggesting disulfidptosis may exist in the pathological process of GC. However, the underlying functions of disulfidptosis regulators in GC remain unknown. The dataset of GSE54129 was screened to comprehensively investigate the disulfidptosis-related diagnostic clusters and immune landscapes in GC. Totally 15 significant disulfidptosis regulators were identified via difference analysis between GC samples and controls. Then random forest model was utilized to assess their importance score (mean decrease Gini). Then a nomogram model was constructed, which could offer benefit to patients based on our subsequent decision curve analysis. All the included GC patients were divided into 2 disulfidptosis subgroups (clusterA and clusterB) according to the significant disulfidptosis regulators in virtue of consensus clustering analysis. The disulfidptosis score of each sample was calculated through PCA algorithms to quantify the disulfidptosis subtypes. Patients from clusterB exhibited lower disulfidptosis scores than those of patients in clusterA. In addition, we found that the cases in clusterB were closely associated with the immunity of activated CD4 T cell, etc., while clusterA was linked to immature dendritic cell, mast cell, natural killer T cell, natural killer cell, etc., which has a higher disulfidptosis score. Therefore, disulfidptosis regulators play an important role in the pathological process of GC, providing a promising marker and an immunotherapeutic strategy for future GC therapy.
二硫键凋亡是一种新型的细胞死亡方式,由 SLC7A11 诱导的二硫键应激介导。胃癌(GC)是一种常见的恶性胃肠道肿瘤。现有证据表明,SLC7A11 可以调节细胞死亡并改善 GC 的进展,这表明二硫键凋亡可能存在于 GC 的病理过程中。然而,GC 中二硫键凋亡调节剂的潜在功能仍然未知。筛选 GSE54129 数据集,全面研究 GC 中二硫键凋亡相关的诊断聚类和免疫景观。通过 GC 样本和对照之间的差异分析,总共确定了 15 个显著的二硫键凋亡调节剂。然后利用随机森林模型评估它们的重要性评分(平均减少基尼系数)。然后构建了一个列线图模型,可以根据我们随后的决策曲线分析为患者提供收益。根据共识聚类分析,所有纳入的 GC 患者根据显著的二硫键凋亡调节剂分为 2 个二硫键凋亡亚组(clusterA 和 clusterB)。通过 PCA 算法计算每个样本的二硫键凋亡评分,以量化二硫键凋亡亚型。发现 clusterB 中的病例与激活的 CD4 T 细胞等免疫密切相关,而 clusterA 与未成熟树突状细胞、肥大细胞、自然杀伤 T 细胞、自然杀伤细胞等有关,其二硫键凋亡评分较高。因此,二硫键凋亡调节剂在 GC 的病理过程中起着重要作用,为未来的 GC 治疗提供了有前途的标志物和免疫治疗策略。