综合生物信息学分析确定了膀胱癌的预后模型和潜在治疗靶点--铁突变相关基因特征。

IF 2.2 4区 医学 Q3 TOXICOLOGY Toxicology Research Pub Date : 2024-01-27 eCollection Date: 2024-02-01 DOI:10.1093/toxres/tfae010
Zonglai Liu, Dan Du, Shizhong Zhang
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引用次数: 0

摘要

背景:膀胱癌(BLCA)是全球发病率最高的癌症之一。铁凋亡是一种新发现的非凋亡性细胞死亡形式,在肿瘤中发挥着重要作用。然而,铁凋亡相关基因(FRGs)在膀胱癌中的预后价值尚未得到充分研究:在本研究中,我们基于 FRGS 进行了共识聚类,并将 BLCA 患者分为 2 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(GO)和 KEGG 通路富集分析对差异表达基因进行了功能注释。蛋白质表达验证在人类蛋白质图谱中得到确认。通过 qPCR 对人类膀胱癌细胞系裂解样本进行基因表达验证:结果:与 C1 相比,C2 具有明显的生存优势和更高的免疫浸润水平。此外,C2 的免疫检查点标记物表达水平也远高于 C1。根据 Cox 和 LASSO 回归分析,建立了一种新型的铁蛋白沉积相关预后特征,可有效预测 BLCA 的预后。根据风险评分划分了高风险组和低风险组。Kaplan-Meier 生存分析表明,在整个队列中,高危组的总生存期短于低危组。此外,还结合风险评分和临床特征绘制了一个提名图。最后,SLC39A7被确定为膀胱癌的潜在靶点:总之,我们在 BLCA 中使用共识聚类发现了两个预后不同的铁浸润簇。我们还建立了一个与铁蛋白沉积相关的预后特征和提名图,它可以指示预后。
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Integrated bioinformatics analysis identifies a Ferroptosis-related gene signature as prognosis model and potential therapeutic target of bladder cancer.

Background: 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.

Method and materials: 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.

Result: 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.

Discussion: 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.

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Toxicology Research
Toxicology Research TOXICOLOGY-
CiteScore
3.60
自引率
0.00%
发文量
82
期刊介绍: A multi-disciplinary journal covering the best research in both fundamental and applied aspects of toxicology
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