Table_5_Identifying a Ferroptosis-Related Gene Signature for Predicting Biochemical Recurrence of Prostate Cancer.XLSX

Ferroptosis induced by lipid peroxidation is closely related to cancer biology. Prostate cancer (PCa) is not only a malignant tumor but also a lipid metabolic disease. Previous studies have identified ferroptosis as an important pathophysiological pathway in PCa development and treatment, but its role in the prognosis of PCa is less well known. In this study, we constructed a nine-ferroptosis-related gene risk model that demonstrated strong prognostic and therapeutic predictive power. The higher risk score calculated by the model was significantly associated with a higher ferroptosis potential index, higher Ki67 expression, higher immune infiltration, higher probability of biochemical recurrence, worse clinicopathological characteristics, and worse response to chemotherapy and antiandrogen therapy in PCa. The mechanisms identified by the gene set enrichment analysis suggested that this signature can accurately distinguish high- and low-risk populations, which is possibly closely related to variations in steroid hormone secretion, regulation of endocrine processes, positive regulation of humoral immune response, and androgen response. Results of this study were confirmed in two independent PCa cohorts, namely, The Cancer Genome Atlas cohort and the MSK-IMPACT Clinical Sequencing Cohort, which contributed to the body of scientific evidence for the prediction of biochemical recurrence in patients with PCa. In addition, as the main components of this signature, the effects of the AIFM2 and NFS1 genes on ferroptosis were evaluated and verified by in vivo and in vitro experiments, respectively. The above findings provided new insights and presented potential clinical applications of ferroptosis in PCa.

脂质过氧化诱导的铁死亡（Ferroptosis）与癌症生物学密切相关。前列腺癌（Prostate cancer, PCa）既是恶性肿瘤，亦是一种脂质代谢性疾病。既往研究已证实铁死亡是前列腺癌发生发展与治疗过程中的重要病理生理通路，但该过程在前列腺癌预后中的作用却鲜为人知。本研究构建了九个铁死亡相关基因风险模型，该模型展现出优异的预后与治疗预测能力。通过该模型计算得到的较高风险评分，与前列腺癌患者更高的铁死亡潜能指数、Ki67表达水平、免疫浸润程度、生化复发概率、较差的临床病理特征，以及对化疗与抗雄激素治疗的不良响应显著相关。基因集富集分析（Gene Set Enrichment Analysis）揭示的机制表明，该基因特征可精准区分高、低风险人群，其潜在机制可能与类固醇激素分泌变异、内分泌过程调控、体液免疫应答正向调控以及雄激素应答密切相关。本研究结果在两个独立的前列腺癌队列中得到验证，分别为癌症基因组图谱（The Cancer Genome Atlas）队列与MSK-IMPACT临床测序队列，这为前列腺癌患者生化复发的预测提供了新的科学依据。此外，作为该基因特征的核心组成部分，本研究分别通过体内外实验，评估并验证了AIFM2与NFS1基因对铁死亡的调控作用。上述研究结果为铁死亡在前列腺癌中的临床应用提供了新的见解与潜在方向。