Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
Genes (Basel). 2022 Jun 16;13(6):1073. doi: 10.3390/genes13061073.
The important roles of machine learning and ferroptosis in bladder cancer (BCa) are still poorly understood. In this study, a comprehensive analysis of 19 ferroptosis-related genes (FRGs) was performed in 1322 patients with BCa from four independent patient cohorts and a pan-cancer cohort of 9824 patients. Twelve FRGs were selected through machine learning algorithm to construct the prognosis model. Significantly differential survival outcomes (hazard ratio (HR) = 2.09, 95% confidence interval (CI): 1.55−2.82, p < 0.0001) were observed between patients with high and low ferroptosis scores in the TCGA cohort, which was also verified in the E-MTAB-4321 cohort (HR = 4.71, 95% CI: 1.58−14.03, p < 0.0001), the GSE31684 cohort (HR = 1.76, 95% CI: 1.08−2.87, p = 0.02), and the pan-cancer cohort (HR = 1.15, 95% CI: 1.07−1.24, p < 0.0001). Tumor immunity-related pathways, including the IL-17 signaling pathway and JAK-STAT signaling pathway, were found to be associated with the ferroptosis score in BCa through a functional enrichment analysis. Further verification in the IMvigor210 cohort revealed the BCa patients with high ferroptosis scores tended to have worse survival outcome after receiving tumor immunotherapy. Significantly different ferroptosis scores could also be found between BCa patients with different reactions to treatment with immune checkpoint inhibitors.
机器学习和铁死亡在膀胱癌（BCa）中的重要作用仍知之甚少。在这项研究中，对来自四个独立患者队列和一个包含 9824 名患者的泛癌队列的 1322 名 BCa 患者进行了 19 个铁死亡相关基因（FRGs）的综合分析。通过机器学习算法选择了 12 个 FRGs 来构建预后模型。在 TCGA 队列中，铁死亡评分高和低的患者之间观察到显著的生存差异结局（风险比（HR）=2.09，95%置信区间（CI）：1.55-2.82，p<0.0001），这在 E-MTAB-4321 队列（HR=4.71，95%CI：1.58-14.03，p<0.0001）、GSE31684 队列（HR=1.76，95%CI：1.08-2.87，p=0.02）和泛癌队列（HR=1.15，95%CI：1.07-1.24，p<0.0001）中也得到了验证。通过功能富集分析发现，肿瘤免疫相关通路，包括 IL-17 信号通路和 JAK-STAT 信号通路，与 BCa 中的铁死亡评分相关。在 IMvigor210 队列中的进一步验证表明，铁死亡评分较高的 BCa 患者在接受肿瘤免疫治疗后生存结局较差。在对免疫检查点抑制剂治疗有不同反应的 BCa 患者之间，也可以发现显著不同的铁死亡评分。
