Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-Constructed By the Province and Ministry, Guangxi Medical University, No. 22, Shuangyong Road, Qingxiu District, Nanning, 530021, Guangxi Zhuang Autonomous Region, China.
Center for Genomic and Personalized Medicine, Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, 530021, Guangxi, China.
Sci Rep. 2024 Jun 19;14(1):14107. doi: 10.1038/s41598-024-61679-y.
Disulfidptosis, a newly identified programmed cell death pathway in prostate cancer (PCa), is closely associated with intracellular disulfide stress and glycolysis. This study aims to elucidate the roles of disulfidptosis-related genes (DRGs) in the pathogenesis and progression of PCa, with the goal of improving diagnostic and therapeutic approaches. We analyzed PCa datasets and normal tissue transcriptome data from TCGA, GEO, and MSKCC. Using consensus clustering analysis and LASSO regression, we developed a risk scoring model, which was validated in an independent cohort. The model's predictive accuracy was confirmed through Kaplan-Meier curves, receiver operating characteristic (ROC) curves, and nomograms. Additionally, we explored the relationship between the risk score and immune cell infiltration, and examined the tumor microenvironment and somatic mutations across different risk groups. We also investigated responses to immunotherapy and drug sensitivity. Our analysis identified two disulfidosis subtypes with significant differences in survival, immune environments, and treatment responses. According to our risk score, the high-risk group exhibited poorer progression-free survival (PFS) and higher tumor mutational burden (TMB), associated with increased immune suppression. Functional enrichment analysis linked high-risk features to key cancer pathways, including the IL-17 signaling pathway. Moreover, drug sensitivity analysis revealed varied responses to chemotherapy, suggesting the potential for disulfidosis-based personalized treatment strategies. Notably, we identified PROK1 as a crucial prognostic marker in PCa, with its reduced expression correlating with disease progression. In summary, our study comprehensively assessed the clinical implications of DRGs in PCa progression and prognosis, offering vital insights for tailored precision medicine approaches.
二硫键程序性细胞死亡（disulfidptosis），一种新发现的前列腺癌（PCa）中细胞内二硫键应激和糖酵解密切相关的程序性细胞死亡途径，本研究旨在阐明二硫键程序性细胞死亡相关基因（DRGs）在 PCa 发病机制和进展中的作用，以期改善诊断和治疗方法。我们分析了 TCGA、GEO 和 MSKCC 中的 PCa 数据集和正常组织转录组数据。通过共识聚类分析和 LASSO 回归，我们开发了一个风险评分模型，并在独立队列中进行了验证。通过 Kaplan-Meier 曲线、受试者工作特征（ROC）曲线和列线图验证了模型的预测准确性。此外，我们还探讨了风险评分与免疫细胞浸润的关系，并研究了不同风险组之间的肿瘤微环境和体细胞突变。我们还研究了对免疫治疗和药物敏感性的反应。我们的分析确定了两种具有显著生存差异、免疫环境和治疗反应差异的二硫键程序性细胞死亡亚型。根据我们的风险评分，高危组的无进展生存期（PFS）更差，肿瘤突变负担（TMB）更高，与免疫抑制增加有关。功能富集分析将高危特征与关键癌症途径联系起来，包括 IL-17 信号通路。此外，药物敏感性分析显示对化疗的反应不同，表明基于二硫键程序性细胞死亡的个性化治疗策略具有潜力。值得注意的是，我们确定了 PROK1 是 PCa 的一个关键预后标志物，其表达降低与疾病进展相关。总之，我们的研究全面评估了 DRGs 在 PCa 进展和预后中的临床意义，为制定个体化精准医学策略提供了重要的见解。
