Sun Jiale, Yue Wenchang, You Jiawei, Wei Xuedong, Huang Yuhua, Ling Zhixin, Hou Jianquan
Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, China.
Department of Urology, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, China.
Front Oncol. 2021 Sep 7;11:730716. doi: 10.3389/fonc.2021.730716. eCollection 2021.
Ferroptosis is a newly found non-apoptotic forms of cell death that plays an important role in tumors. However, the prognostic value of ferroptosis-related genes (FRG) in bladder cancer (BLCA) have not been well examined.
FRG data and clinical information were collected from The Cancer Genome Atlas (TCGA). Then, significantly different FRGs were investigated by functional enrichment analyses. The prognostic FRG signature was identified by univariate cox regression and least absolute shrinkage and selection operator (LASSO) analysis, which was validated in TCGA cohort and Gene Expression Omnibus (GEO) cohort. Subsequently, the nomogram integrating risk scores and clinical parameters were established and evaluated. Additionally, Gene Set Enrichment Analyses (GSEA) was performed to explore the potential molecular mechanisms underlying our prognostic FRG signature. Finally, the expression of three key FRGs was verified in clinical specimens.
Thirty-two significantly different FRGs were identified from TCGA-BLCA cohort. Enrichment analyses showed that these genes were mainly related to the ferroptosis. Seven genes (TFRC, G6PD, SLC38A1, ZEB1, SCD, SRC, and PRDX6) were then identified to develop a prognostic signature. The Kaplan-Meier analysis confirmed the predictive value of the signature for overall survival (OS) in both TCGA and GEO cohort. A nomogram integrating age and risk scores was established and demonstrated high predictive accuracy, which was validated through calibration curves and receiver operating characteristic (ROC) curve [area under the curve (AUC) = 0.690]. GSEA showed that molecular alteration in the high- or low-risk group was closely associated with ferroptosis. Finally, experimental results confirmed the expression of SCD, SRC, and PRDX6 in BLCA.
Herein, we identified a novel FRG prognostic signature that maybe involved in BLCA. It showed high values in predicting OS, and targeting these FRGs may be an alternative for BLCA treatment. Further experimental studies are warranted to uncover the mechanisms that these FRGs mediate BLCA progression.
铁死亡是一种新发现的非凋亡性细胞死亡形式，在肿瘤中起重要作用。然而，铁死亡相关基因（FRG）在膀胱癌（BLCA）中的预后价值尚未得到充分研究。
从癌症基因组图谱（TCGA）收集FRG数据和临床信息。然后，通过功能富集分析研究显著不同的FRG。通过单变量cox回归和最小绝对收缩和选择算子（LASSO）分析确定预后FRG特征，并在TCGA队列和基因表达综合数据库（GEO）队列中进行验证。随后，建立并评估整合风险评分和临床参数的列线图。此外，进行基因集富集分析（GSEA）以探索我们的预后FRG特征潜在的分子机制。最后，在临床标本中验证三个关键FRG的表达。
从TCGA - BLCA队列中鉴定出32个显著不同的FRG。富集分析表明这些基因主要与铁死亡相关。然后鉴定出七个基因（TFRC、G6PD、SLC38A1、ZEB1、SCD、SRC和PRDX6）以建立预后特征。Kaplan - Meier分析证实了该特征在TCGA和GEO队列中对总生存期（OS）的预测价值。建立了整合年龄和风险评分的列线图，并显示出高预测准确性，通过校准曲线和受试者工作特征（ROC）曲线[曲线下面积（AUC）= 0.690]进行了验证。GSEA表明高风险或低风险组中的分子改变与铁死亡密切相关。最后，实验结果证实了SCD、SRC和PRDX6在BLCA中的表达。
在此，我们鉴定出一种可能参与BLCA的新型FRG预后特征。它在预测OS方面具有很高价值，靶向这些FRG可能是BLCA治疗的一种选择。有必要进行进一步的实验研究以揭示这些FRG介导BLCA进展的机制。
