Department of Urology, Urology Research Institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China.
Department of Urology, National Regional Medical Centre, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China.
Biol Direct. 2024 Oct 23;19(1):97. doi: 10.1186/s13062-024-00544-4.
Disulfidptosis refers to cell death caused by the accumulation and bonding of disulfide in the cytoskeleton protein of SLC7A11-high level cells under glucose deprivation. However, the role of disulfidptosis-related genes (DRGs) in prostate cancer (PCa) classification and regulation of the tumor microenvironment remains unclear.
Firstly, we analyzed the expression and mutation landscape of DRGs in PCa. We observed the expression levels of SLC7A11 in PCa cells through in vitro experiments and assessed the inhibitory effect of the glucose transporter inhibitor BAY-876 on SLC7A11-high cells using CCK-8 assay. Subsequently, we performed unsupervised clustering of the PCa population and analyzed the differentially expressed genes (DEGs) between clusters. Using machine learning techniques to select a minimal gene set and developed disulfidoptosis-related risk signatures for PCa. We analyzed the tumor immune microenvironment and the sensitivity to immunotherapy in different risk groups. Finally, we validated the accuracy of the prognostic signatures genes using single-cell sequencing, qPCR, and western blot.
Although SLC7A11 can increase the migration ability of tumor cells, BAY-876 effectively suppressed the viability of prostate cancer cells, particularly those with high SLC7A11 expression. Based on the DRGs, PCa patients were categorized into two clusters (A and B). The risk label, consisting of a minimal gene set derived from DEGs, included four genes. The expression levels of these genes in PCa were initially validated through in vitro experiments, and the accuracy of the risk label was confirmed in an external dataset. Cluster-B exhibited higher expression levels of DRG, representing lower risk, better prognosis, higher immune cell infiltration, and greater sensitivity to immune checkpoint blockade, whereas Cluster A showed the opposite results. These findings suggest that DRGs may serve as targets for PCa classification and treatment. Additionally, we constructed a nomogram that incorporates DRGs and clinical pathological features, providing clinicians with a quantitative method to assess the prognosis of PCa patients.
This study analyzed the potential connection between disulfidptosis and PCa, and established a prognostic model related to disulfidptosis, which holds promise as a valuable tool for the management and treatment of PCa patients.
细胞在葡萄糖缺乏时，细胞骨架蛋白中的巯基积累和键合导致 SLC7A11 高表达细胞发生细胞死亡，称为二硫键细胞死亡。然而，二硫键细胞死亡相关基因（DRGs）在前列腺癌（PCa）分类和肿瘤微环境调控中的作用尚不清楚。
首先，我们分析了 DRGs 在 PCa 中的表达和突变情况。通过体外实验观察了 PCa 细胞中 SLC7A11 的表达水平，并通过 CCK-8 检测评估了葡萄糖转运体抑制剂 BAY-876 对 SLC7A11 高表达细胞的抑制作用。随后，我们对 PCa 人群进行无监督聚类，并分析了聚类间差异表达基因（DEGs）。使用机器学习技术选择最小基因集，并为 PCa 开发二硫键细胞死亡相关风险特征。我们分析了不同风险组的肿瘤免疫微环境和对免疫治疗的敏感性。最后，我们使用单细胞测序、qPCR 和 Western blot 验证了预后特征基因的准确性。
虽然 SLC7A11 可以增加肿瘤细胞的迁移能力，但 BAY-876 能有效抑制前列腺癌细胞的活力，特别是高 SLC7A11 表达的细胞。基于 DRGs，将 PCa 患者分为两个亚群（A 和 B）。风险标签由来自 DEGs 的最小基因集组成，包括四个基因。这些基因在 PCa 中的表达水平首先通过体外实验进行验证，并在外部数据集得到了风险标签的准确性验证。B 簇表现出更高的 DRG 表达水平，代表着更低的风险、更好的预后、更高的免疫细胞浸润和对免疫检查点阻断的更高敏感性，而 A 簇则表现出相反的结果。这些发现表明，DRGs 可能成为 PCa 分类和治疗的靶点。此外，我们构建了一个包含 DRGs 和临床病理特征的诺莫图，为临床医生提供了一种定量评估 PCa 患者预后的方法。
本研究分析了二硫键细胞死亡与 PCa 之间的潜在联系，并建立了与二硫键细胞死亡相关的预后模型，有望成为 PCa 患者管理和治疗的有价值工具。
