Liu Zonglai, Du Dan, Zhang Shizhong
Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, No. 8, University Avenue, Yichang 443002, Hubei Province, China.
Medical College, China Three Gorges University, No. 8, University Avenue, Yichang 443002, Hubei Province, China.
Toxicol Res (Camb). 2024 Jan 27;13(1):tfae010. doi: 10.1093/toxres/tfae010. eCollection 2024 Feb.
Bladder cancer (BLCA) is one of the most prevalent cancers worldwide. Ferroptosis is a newly discovered form of non-apoptotic cell death that plays an important role in tumors. However, the prognostic value of ferroptosis-related genes (FRGs) in BLCA has not yet been well studied.
In this study, we performed consensus clustering based on FRGS and categorized BLCA patients into 2 clusters (C1 and C2). Immune cell infiltration score and immune score for each sample were computed using the CIBERSORT and ESTIMATE methods. Functional annotation of differentially expressed genes were performed by Gene Ontology (GO) and KEGG pathway enrichment analysis. Protein expression validation were confirmed in Human Protein Atlas. Gene expression validation were performed by qPCR in human bladder cancer cell lines lysis samples.
C2 had a significant survival advantage and higher immune infiltration levels than C1. Additionally, C2 showed substantially higher expression levels of immune checkpoint markers than C1. According to the Cox and LASSO regression analyses, a novel ferroptosis-related prognostic signature was developed to predict the prognosis of BLCA effectively. High-risk and low-risk groups were divided according to risk scores. Kaplan-Meier survival analyses showed that the high-risk group had a shorter overall survival than the low-risk group throughout the cohort. Furthermore, a nomogram combining risk score and clinical features was developed. Finally, SLC39A7 was identified as a potential target in bladder cancer.
In conclusion, we identified two ferroptosis-clusters with different prognoses using consensus clustering in BLCA. We also developed a ferroptosis-related prognostic signature and nomogram, which could indicate the outcome.
膀胱癌（BLCA）是全球最常见的癌症之一。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（FRGs）在BLCA中的预后价值尚未得到充分研究。
在本研究中，我们基于FRGs进行了一致性聚类，并将BLCA患者分为两个聚类（C1和C2）。使用CIBERSORT和ESTIMATE方法计算每个样本的免疫细胞浸润评分和免疫评分。通过基因本体论（GO）和KEGG通路富集分析对差异表达基因进行功能注释。在人类蛋白质图谱中确认蛋白质表达验证。通过qPCR在人膀胱癌细胞系裂解样本中进行基因表达验证。
C2具有显著的生存优势，且免疫浸润水平高于C1。此外，C2显示免疫检查点标志物的表达水平明显高于C1。根据Cox和LASSO回归分析，开发了一种新的铁死亡相关预后特征，以有效预测BLCA的预后。根据风险评分分为高风险组和低风险组。Kaplan-Meier生存分析表明，在整个队列中，高风险组的总生存期短于低风险组。此外，还开发了一种结合风险评分和临床特征的列线图。最后，SLC39A7被确定为膀胱癌的潜在靶点。
总之，我们在BLCA中使用一致性聚类鉴定出两个具有不同预后的铁死亡聚类。我们还开发了一种铁死亡相关预后特征和列线图，可指示预后。
