A novel ferroptosis-related gene prognostic index for prognosis and response to immunotherapy in patients with prostate cancer.
A novel ferroptosis-related gene prognostic index for prognosis and response to immunotherapy in patients with prostate cancer.
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一种新的铁死亡相关基因预后指数，用于前列腺癌患者的预后和免疫治疗反应
DOI：
10.3389/fendo.2022.975623
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发表时间：
2022
影响因子：
5.2
通讯作者：
中科院分区：
文献类型：
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作者：
前列腺癌（PCa）是全球癌症死亡的主要原因之一。铁凋亡是指一种铁依赖性形式的调节性细胞死亡，并参与前列腺肿瘤的发生。已经开发了一些铁中毒相关的基因标签来预测PCa患者的预后。然而，以前的特征通常是基于生化无复发生存期建立的，这已被证明不是总生存期（OS）的良好替代品。本研究旨在构建一种新的铁凋亡相关基因预后指数（FRGPI），用于预测PCa患者根治性前列腺切除术后的无病生存期（DFS）和免疫治疗反应。PCa患者的基因表达和临床病理数据来自TCGA数据库。通过深入的生物信息学分析，使用基于功能富集、一致聚类、加权基因共表达网络分析（WGCNA）和蛋白质-蛋白质相互作用（PPI）网络构建的新颖和全面的算法，确定了与PCa患者DFS相关的铁蛋白沉积症相关的枢纽基因。FRGPI是基于使用多变量考克斯回归分析选择的基因建立的，并在另外两个PCa队列中进一步验证。接下来，对FRGPI高和FRGPI低亚组的临床病理、分子和免疫特征进行了表征和比较。最后，使用抗PD-L1药物治疗的转移性尿路上皮癌队列评估FRGPI对免疫治疗反应的预测作用。FRGPI是基于四个基因（E2 F1，CDC 20，TYMS和NUP 85）构建的，FRGPI高的患者比FRGPI低的患者具有更差的DFS。多因素考克斯回归分析显示，FRGPI可作为PCa患者根治术后的独立预后因素。建立了一个包含FRGPI和其他临床病理参数的预后诺模图，以定量预测PCa患者的DFS。此外，综合结果表明，高FRGPI评分与更差的临床病理特征、更高的突变计数、拷贝数变异（CNVs）频率增加、更高的同源重组缺陷（HRD）和免疫评分、更高的mRNAsi以及更重要的是，对免疫治疗的敏感性增强呈显著正相关。FRGPI不仅是一个有前途的和强大的预后生物标志物，也是一个潜在的指标，免疫预后的PCa患者根治性切除术后。
Prostate cancer (PCa) is among the leading causes of cancer death worldwide. Ferroptosis refers to an iron-dependent form of regulated cell death and is involved in prostate tumorigenesis. A few ferroptosis-related gene signatures have been developed to predict the prognosis for PCa patients. However, previous signatures were typically established based on biochemical recurrence-free survival, which has proven not to be a good surrogate for overall survival (OS). This study aimed to construct a novel ferroptosis-related gene prognostic index (FRGPI) to predict disease-free survival (DFS) and response to immunotherapy for PCa patients after radical prostatectomy. Gene expression and clinicopathological data on PCa patients were obtained from the TCGA database. Ferroptosis-related hub genes associated with DFS of PCa patients were identified by an in-depth bioinformatics analysis using a novel and comprehensive algorithm based on functional enrichment, consensus clustering, weighted gene co-expression network analysis (WGCNA), and protein-protein interaction (PPI) network construction. The FRGPI was established on the basis of the genes selected using multivariate cox regression analysis and further validated in two additional PCa cohorts. Next, the clinicopathological, molecular, and immune profiles were characterized and compared between FRGPI-high and FRGPI-low subgroups. Finally, the predictive role of the FRGPI in response to immunotherapy was estimated using a metastatic urothelial cancer cohort treated with an anti-PD-L1 agent. The FRGPI was constructed based on four genes (E2F1, CDC20, TYMS, and NUP85), and FRGPI-high patients had worse DFS than FRGPI-low patients. Multivariate cox regression analysis revealed that FRGPI could act as an independent prognostic factor for PCa patients after radical prostatectomy. A prognostic nomogram comprising the FRGPI and other clinicopathological parameters was established to predict the DFS for PCa patients quantitatively. In addition, comprehensive results demonstrated that high FRGPI scores showed a significantly positive correlation with worse clinicopathological features, higher mutation counts, increased frequency of copy number variations (CNVs), higher homologous recombination deficiency (HRD) and immune scores, higher mRNAsi, and more importantly, enhanced sensitivity to immunotherapy. FRGPI is not only a promising and robust prognostic biomarker, but also a potential indicator of immunotherapeutic outcomes for PCa patients after radical prostatectomy.
DOI：
10.1016/j.ijrobp.2010.08.013
发表时间：
2011-02-01
影响因子：
7
作者：
Udayakumar, Thirupandiyur S.;Stoyanova, Radka;Hachem, Paul;Ahmed, Mansoor M.;Pollack, Alan
通讯作者：
Pollack, Alan