The Sixth Clinical Medical School, Affiliated Qingyuan Hospital, Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, China.
J Mol Neurosci. 2024 Apr 4;74(2):38. doi: 10.1007/s12031-024-02216-4.
Disulfidptosis is a newly discovered form of regulatory cell death. However, the identification of disulfidptosis-related molecular subtypes and potential biomarkers in gliomas and their prognostic predictive potential need to be further elucidated. RNA sequencing profiles and the relevant clinical data were obtained from the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). Disulfidptosis-related clusters were identified by unsupervised clustering analysis. Immune cell infiltration analysis and drug sensitivity analysis were used to explore the differences between clusters. Gene set enrichment analysis (GSEA) of differential genes between clusters was performed to explore the potential biological functions and signaling. A disulfidptosis-related scoring system (DRSS) was constructed based on a combined COX and LASSO analysis. Mendelian randomization (MR) analyses were used to further explore the causal relationship between levels of genes in DRSS and an increased risk of glioma. A prognosis nomogram was constructed based on the DRSS and 3 clinical features (age, WHO stage, and IDH status). The accuracy and stability of the prognosis nomogram were also validated in different cohorts. We identified two clusters that exhibited different prognoses, drug sensitivity profiles, and tumor microenvironment infiltration profiles. The overall survival (OS) of Cluster2 was significantly better than Cluster1. Cluster1 had an overall greater infiltration of immune cells compared to Cluster2. However, the Monocytes, activated B cells had higher infiltration abundance in Cluster2. GSEA results showed significant enrichment of immune-related biological processes in Cluster1, while Cluster2 was more enriched for functions related to neurotransmission and regulation. PER3, RAB34, NKX3-2, GPX7, FRA10AC1, and TGIF1 were finally included to construct DRSS. DRSS was independently related to prognosis. There was a significant difference in overall survival between the low-risk score group and the high-risk score group. Among six genes in DRSS, GPX7 levels were demonstrated to have a causal relationship with an increased risk of glioma. GPX7 may become a more promising biomarker for gliomas. The prognosis nomogram constructed based on the DRSS and three clinical features has considerable potential for predicting the prognosis of patients with glioma. Free online software for implementing this nomogram was established: https://yekun-zhuang.shinyapps.io/DynNomapp/ . Our study established a novel glioma classification based on the disulfidptosis-related molecular subtypes. We constructed the DRSS and the prognosis nomogram to accurately stratify the prognosis of glioma patients. GPX7 was identified as a more promising biomarker for glioma. We provide important insights into the treatment and prognosis of gliomas.
二硫键凋亡是一种新发现的调节性细胞死亡形式。然而，需要进一步阐明胶质瘤中二硫键凋亡相关分子亚型和潜在生物标志物的鉴定及其预后预测潜力。从癌症基因组图谱（TCGA）和中国胶质瘤基因组图谱（CGGA）获得了 RNA 测序图谱和相关临床数据。通过无监督聚类分析确定二硫键凋亡相关聚类。免疫细胞浸润分析和药物敏感性分析用于探索聚类之间的差异。对聚类之间差异基因进行基因集富集分析（GSEA），以探讨潜在的生物学功能和信号通路。基于 COX 和 LASSO 联合分析构建二硫键凋亡相关评分系统（DRSS）。孟德尔随机分析（MR）用于进一步探讨 DRSS 中基因水平与胶质瘤风险增加之间的因果关系。基于 DRSS 和 3 个临床特征（年龄、WHO 分期和 IDH 状态）构建预后列线图。还在不同队列中验证了预后列线图的准确性和稳定性。我们确定了两个具有不同预后、药物敏感性谱和肿瘤微环境浸润谱的聚类。Cluster2 的总生存期（OS）明显优于 Cluster1。与 Cluster2 相比，Cluster1 的免疫细胞总体浸润程度更高。然而，Cluster2 中单核细胞、活化 B 细胞的浸润丰度更高。GSEA 结果表明，Cluster1 中显著富集了与免疫相关的生物学过程，而 Cluster2 则更富集与神经传递和调节相关的功能。最终纳入 PER3、RAB34、NKX3-2、GPX7、FRA10AC1 和 TGIF1 构建 DRSS。DRSS 与预后独立相关。低风险评分组和高风险评分组之间的总生存率有显著差异。在 DRSS 的六个基因中，GPX7 水平与胶质瘤风险增加有因果关系。GPX7 可能成为更有前途的神经胶质瘤生物标志物。基于 DRSS 和三个临床特征构建的预后列线图具有预测胶质瘤患者预后的巨大潜力。建立了用于实现此列线图的免费在线软件：https://yekun-zhuang.shinyapps.io/DynNomapp/。本研究基于二硫键凋亡相关分子亚型建立了一种新的胶质母细胞瘤分类方法。我们构建了 DRSS 和预后列线图，以准确分层胶质瘤患者的预后。鉴定出 GPX7 是一种更有前途的神经胶质瘤生物标志物。为胶质母细胞瘤的治疗和预后提供了重要见解。
