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基于铁死亡相关基因的膀胱癌生存预测新模型的建立与验证。

Development and validation of a novel model for predicting the survival of bladder cancer based on ferroptosis-related genes.

机构信息

Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China.

Department of Urology, Dongying People's Hospital, Dongying, Shandong 257091, China.

出版信息

Aging (Albany NY). 2022 Nov 17;14(22):9037-9055. doi: 10.18632/aging.204385.


DOI:10.18632/aging.204385
PMID:36399105
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9740359/
Abstract

The role of ferroptosis, a new form of cell death, in bladder cancer (BC) has not been sufficiently studied. This study aimed to establish a prognostic prediction model for BC patients based on the expression profile of ferroptosis-related genes (FRG). The expression profiles of BC samples with clinical information were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). A total of 80 differentially expressed genes (DEGs) related to FRG were identified among which 37 DEGs were found to have a prognostic value. Eleven genetic markers including SLC2A12, CDO1, JDP2, MAFG, CAPG, RRM2, SLC2A3, SLC3A2, VDAC2, GCH1, and ANGPTL7 were identified through the LASSO regression analysis. The ROC curve analysis showed that the AUC was 0.702, 0.664, and 0.655 for the 1-year, 3-year, and 5-year survival outcomes, respectively. The prediction performance was verified in the TCGA-testing set and external set GSE13507. Multivariate Cox proportional hazards analysis showed that the risk score was an independent prognostic predictor. Moreover, we found differences in gene mutation, gene expression, and immune cell infiltration between the high and low-risk groups of BC patients. Finally, a nomogram was constructed by integrating clinical features and FRG signatures to predict the survival outcomes of BC patients. In addition, the differential expression of FRG mRNA and protein was verified through PCR and HPA online site. The characteristics of 11 FRG genes were examined and a prognostic nomogram for predicting the overall survival of BC was established.

摘要

铁死亡作为一种新的细胞死亡形式,在膀胱癌(BC)中的作用尚未得到充分研究。本研究旨在基于铁死亡相关基因(FRG)的表达谱,为 BC 患者建立一个预后预测模型。从癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)中获得了具有临床信息的 BC 样本的表达谱。在这些样本中,共鉴定出 80 个与 FRG 相关的差异表达基因(DEGs),其中 37 个 DEGs 具有预后价值。通过 LASSO 回归分析,鉴定出 11 个遗传标志物,包括 SLC2A12、CDO1、JDP2、MAFG、CAPG、RRM2、SLC2A3、SLC3A2、VDAC2、GCH1 和 ANGPTL7。ROC 曲线分析表明,1 年、3 年和 5 年生存率的 AUC 分别为 0.702、0.664 和 0.655。该预测模型在 TCGA 测试集和外部数据集 GSE13507 中得到了验证。多变量 Cox 比例风险分析表明,风险评分是独立的预后预测因子。此外,我们发现 BC 患者高、低风险组之间存在基因突变、基因表达和免疫细胞浸润的差异。最后,通过整合临床特征和 FRG 特征构建了一个列线图,以预测 BC 患者的生存结局。此外,通过 PCR 和 HPA 在线网站验证了 FRG mRNA 和蛋白的差异表达。检查了 11 个 FRG 基因的特征,并建立了一个预测 BC 总体生存率的预后列线图。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4635/9740359/c7bbddaf7d51/aging-14-204385-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4635/9740359/4c2f998c8137/aging-14-204385-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4635/9740359/12b542ce64de/aging-14-204385-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4635/9740359/f82e57d6560a/aging-14-204385-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4635/9740359/44bb33e9603d/aging-14-204385-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4635/9740359/606231362e45/aging-14-204385-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4635/9740359/5f574f0012e8/aging-14-204385-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4635/9740359/84376353aede/aging-14-204385-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4635/9740359/c7bbddaf7d51/aging-14-204385-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4635/9740359/4c2f998c8137/aging-14-204385-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4635/9740359/12b542ce64de/aging-14-204385-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4635/9740359/f82e57d6560a/aging-14-204385-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4635/9740359/44bb33e9603d/aging-14-204385-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4635/9740359/606231362e45/aging-14-204385-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4635/9740359/5f574f0012e8/aging-14-204385-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4635/9740359/84376353aede/aging-14-204385-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4635/9740359/c7bbddaf7d51/aging-14-204385-g008.jpg

相似文献

[1]
Development and validation of a novel model for predicting the survival of bladder cancer based on ferroptosis-related genes.

Aging (Albany NY). 2022-11-17

[2]
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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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引用本文的文献

[1]
A comprehensive investigation of PRMT5 in the prognosis and ion channel features of lung cancer.

Front Oncol. 2024-11-29

[2]
Ferroptosis: An Emerging Target for Bladder Cancer Therapy.

Curr Issues Mol Biol. 2023-10-10

[3]
Identifying stage-associated hub genes in bladder cancer via weighted gene co-expression network and robust rank aggregation analyses.

Medicine (Baltimore). 2022-12-23

本文引用的文献

[1]
Management, Surveillance Patterns, and Costs Associated With Low-Grade Papillary Stage Ta Non-Muscle-Invasive Bladder Cancer Among Older Adults, 2004-2013.

JAMA Netw Open. 2022-3-1

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Cancer Commun (Lond). 2022-2

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CA Cancer J Clin. 2022-1

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Biological Functions and Prognostic Value of Ferroptosis-Related Genes in Bladder Cancer.

Front Mol Biosci. 2021-11-17

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Ferroptosis Meets Cell-Cell Contacts.

Cells. 2021-9-17

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J Exp Med. 2021-6-7

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JAMA. 2020-11-17

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CA Cancer J Clin. 2020-9

[9]
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Signal Transduct Target Ther. 2020-6-30

[10]
The Application of Ferroptosis in Diseases.

Pharmacol Res. 2020-9

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