Abstract：
Bladder cancer (BLCA) is a malignant urothelial carcinoma with a high mortality rate. Ferroptosis is a new type of programmed cell death and functions in suppressing tumor growth and progression. However, few studies focus on ferroptosis and BLCA.
We explored the potential oncogenic roles of ferroptosis-related genes in BLCA based on multiple public datasets. We then used univariate and multivariate cox regression to build a new survival model based on ferroptosis-related genes to predict the survival of BLCA.
We found that 23 ferroptosis-related genes had a strong correlation with each other in BLCA. Eight ferroptosis-related genes, CDKN1A, HSPA5, NFE2L2, MT1G, FANCD2, CISD1, TFRC, NCOA4, had a significantly different expression and heat-map. HSPA5 and CISD1 have a statistically significant difference in OS and DFS. Besides, CISD1 had an ideal nomogram to predict the 1-3-5-year OS (C-index: 0.701, P < .001). Furthermore, HSPA5 and CISD1 had a lower DNA methylation rate than normal tissue and HSPA5 had a positive connection with TMB (P = .02). In addition, HSPA5 participated in the DNA replication and P53 signaling pathway, and CISD1 mediated the oxidative phosphorylation and positive regulation of the intrinsic apoptotic signaling pathway.
Ferroptosis-related genes had a strong correlation with BLCA, notably, HSPA5 and CISD1 may play a role in inducing ferroptosis to suppress bladder tumorigenesis and CISD1 can be a novel prognostic biomarker as well as an effective target for diagnosis and treatment in BLCA.
We explored the potential oncogenic roles of ferroptosis-related genes in BLCA based on multiple public datasets. We then used univariate and multivariate cox regression to build a new survival model based on ferroptosis-related genes to predict the survival of BLCA.
We found that 23 ferroptosis-related genes had a strong correlation with each other in BLCA. Eight ferroptosis-related genes, CDKN1A, HSPA5, NFE2L2, MT1G, FANCD2, CISD1, TFRC, NCOA4, had a significantly different expression and heat-map. HSPA5 and CISD1 have a statistically significant difference in OS and DFS. Besides, CISD1 had an ideal nomogram to predict the 1-3-5-year OS (C-index: 0.701, P < .001). Furthermore, HSPA5 and CISD1 had a lower DNA methylation rate than normal tissue and HSPA5 had a positive connection with TMB (P = .02). In addition, HSPA5 participated in the DNA replication and P53 signaling pathway, and CISD1 mediated the oxidative phosphorylation and positive regulation of the intrinsic apoptotic signaling pathway.
Ferroptosis-related genes had a strong correlation with BLCA, notably, HSPA5 and CISD1 may play a role in inducing ferroptosis to suppress bladder tumorigenesis and CISD1 can be a novel prognostic biomarker as well as an effective target for diagnosis and treatment in BLCA.
摘要：
膀胱癌（BLCA）是一种恶性尿路上皮癌，死亡率高。Ferroptosis是一种新型的程序性细胞死亡，具有抑制肿瘤生长和进展的功能。然而,很少有研究集中在铁凋亡和BLCA。
我们基于多个公开数据集探索了BLCA中铁凋亡相关基因的潜在致癌作用。然后，我们使用单变量和多变量cox回归建立了基于铁凋亡相关基因的新生存模型来预测BLCA的生存。
我们发现在BLCA中23个与铁凋亡相关的基因彼此具有很强的相关性。八个铁死亡相关基因，CDKN1A,HSPA5,NFE2L2,MT1G,FANCD2，CISD1，TFRC，NCOA4具有显著不同的表达和热图。HSPA5和CISD1在OS和DFS上有统计学上的显著差异。此外,CISD1有一个理想的列线图来预测1-3-5年的OS（C指数：0.701，P<.001）。此外，HSPA5和CISD1的DNA甲基化率低于正常组织，HSPA5与TMB呈正相关（P=0.02）。此外,HSPA5参与DNA复制和P53信号通路,和CISD1介导内源性凋亡信号通路的氧化磷酸化和正调节。
铁凋亡相关基因与BLCA有很强的相关性，特别是,HSPA5和CISD1可能在诱导铁凋亡以抑制膀胱肿瘤发生中起作用，CISD1可能是一种新型的预后生物标志物，也是BLCA诊断和治疗的有效靶标。
我们基于多个公开数据集探索了BLCA中铁凋亡相关基因的潜在致癌作用。然后，我们使用单变量和多变量cox回归建立了基于铁凋亡相关基因的新生存模型来预测BLCA的生存。
我们发现在BLCA中23个与铁凋亡相关的基因彼此具有很强的相关性。八个铁死亡相关基因，CDKN1A,HSPA5,NFE2L2,MT1G,FANCD2，CISD1，TFRC，NCOA4具有显著不同的表达和热图。HSPA5和CISD1在OS和DFS上有统计学上的显著差异。此外,CISD1有一个理想的列线图来预测1-3-5年的OS（C指数：0.701，P<.001）。此外，HSPA5和CISD1的DNA甲基化率低于正常组织，HSPA5与TMB呈正相关（P=0.02）。此外,HSPA5参与DNA复制和P53信号通路,和CISD1介导内源性凋亡信号通路的氧化磷酸化和正调节。
铁凋亡相关基因与BLCA有很强的相关性，特别是,HSPA5和CISD1可能在诱导铁凋亡以抑制膀胱肿瘤发生中起作用，CISD1可能是一种新型的预后生物标志物，也是BLCA诊断和治疗的有效靶标。
