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通过生物信息学和组织芯片分析发现,FDX1表达可预测透明细胞肾细胞癌的良好预后。

FDX1 expression predicts favourable prognosis in clear cell renal cell carcinoma identified by bioinformatics and tissue microarray analysis.

作者信息

Huang Xing, Wang Tao, Ye Jiali, Feng Huayi, Zhang Xiangyi, Ma Xin, Wang Baojun, Huang Yan, Zhang Xu

机构信息

Senior Department of Urology, The Third Medical Centre of PLA General Hospital, Beijing, China.

Medical School of Chinese PLA, Beijing, China.

出版信息

Front Genet. 2022 Sep 16;13:994741. doi: 10.3389/fgene.2022.994741. eCollection 2022.


DOI:10.3389/fgene.2022.994741
PMID:36186457
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9523472/
Abstract

Ferredoxin 1 (FDX1), an iron-sulphur protein, is responsible for electron transfer in a range of metabolic redox reactions. Clear cell renal cell carcinoma (ccRCC) is an aggressive cancer characterised by metabolic reprogramming, and FDX1 is a critical regulator of cuproptosis. However, the expression profile and prognostic value of FDX1 associated with clinicopathological features in ccRCC remain largely unelucidated. In this study, we integrated a series of public bioinformatic analysis to explore the mRNA and protein profiles of FDX1 across human cancers and cell lines and validated its expression and prognostic value, especially in ccRCC. In this study, FDX1 mRNA and protein expression were aberrantly downregulated and associated with ccRCC grade, stage, and nodal metastasis, whereas in adjacent non-tumour kidney tissue, it was abundantly expressed and cytoplasmically localised in renal tubular epithelial cells. Multivariate analysis indicated that low FDX1 expression contributed to unfavourable overall and disease-free survival. The functional enrichment of FDX1 co-expressed genes in ccRCC involved mainly mitochondrial dysfunction in various metabolic processes and biological oxidation, besides iron-sulphur cluster biogenesis. Furthermore, FDX1 modulates immunological infiltration to affect prognosis. Thus, FDX1 downregulation is mechanistically because of ccRCC tumourigenesis and is a promising prognostic biomarker to stratify patients with ccRCC.

摘要

铁氧化还原蛋白1(FDX1)是一种铁硫蛋白,负责一系列代谢氧化还原反应中的电子传递。透明细胞肾细胞癌(ccRCC)是一种具有代谢重编程特征的侵袭性癌症,而FDX1是铜死亡的关键调节因子。然而,FDX1在ccRCC中的表达谱及其与临床病理特征相关的预后价值在很大程度上仍未阐明。在本研究中,我们整合了一系列公共生物信息学分析,以探索FDX1在人类癌症和细胞系中的mRNA和蛋白质谱,并验证其表达及预后价值,特别是在ccRCC中的情况。在本研究中,FDX1的mRNA和蛋白质表达异常下调,且与ccRCC的分级、分期和淋巴结转移相关,而在相邻的非肿瘤肾组织中,它在肾小管上皮细胞中大量表达且定位于细胞质中。多变量分析表明,低FDX1表达导致总体生存率和无病生存率不佳。在ccRCC中,与FDX1共表达的基因的功能富集主要涉及各种代谢过程和生物氧化中的线粒体功能障碍,以及铁硫簇生物发生。此外,FDX1调节免疫浸润以影响预后。因此,FDX1下调在机制上归因于ccRCC的肿瘤发生,并且是对ccRCC患者进行分层的有前景的预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b66f/9523472/e7c4e4a20f9d/fgene-13-994741-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b66f/9523472/0d933295ea5d/fgene-13-994741-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b66f/9523472/798c57e40383/fgene-13-994741-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b66f/9523472/b70c0daeaf41/fgene-13-994741-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b66f/9523472/8fa8cbb00088/fgene-13-994741-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b66f/9523472/de9f9aa86c2d/fgene-13-994741-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b66f/9523472/2c2089bba99d/fgene-13-994741-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b66f/9523472/7b2bae3fdf24/fgene-13-994741-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b66f/9523472/e7c4e4a20f9d/fgene-13-994741-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b66f/9523472/0d933295ea5d/fgene-13-994741-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b66f/9523472/798c57e40383/fgene-13-994741-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b66f/9523472/b70c0daeaf41/fgene-13-994741-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b66f/9523472/8fa8cbb00088/fgene-13-994741-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b66f/9523472/de9f9aa86c2d/fgene-13-994741-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b66f/9523472/2c2089bba99d/fgene-13-994741-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b66f/9523472/7b2bae3fdf24/fgene-13-994741-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b66f/9523472/e7c4e4a20f9d/fgene-13-994741-g008.jpg

相似文献

[1]
FDX1 expression predicts favourable prognosis in clear cell renal cell carcinoma identified by bioinformatics and tissue microarray analysis.

Front Genet. 2022-9-16

[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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[2]
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[3]
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Int J Mol Med. 2025-8

[4]
Cuproptosis: the mechanisms of copper-induced cell death and its implication in colorectal cancer.

Naunyn Schmiedebergs Arch Pharmacol. 2025-5-21

[5]
Unveiling the Cuproptosis in Colitis and Colitis-Related Carcinogenesis: A Multifaceted Player and Immune Moderator.

Research (Wash D C). 2025-5-14

[6]
Impact of diabetes and metformin on cuproptosis and ferroptosis in breast cancer patients: an immunohistochemical analysis.

Discov Oncol. 2025-4-29

[7]
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Sci Rep. 2025-3-15

[8]
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Mol Cancer. 2024-11-15

[9]
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[10]
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本文引用的文献

[1]
A Novel Cuproptosis-Related Prognostic Gene Signature and Validation of Differential Expression in Clear Cell Renal Cell Carcinoma.

Genes (Basel). 2022-5-10

[2]
Selective Targeting of Cancer Cells by Copper Ionophores: An Overview.

Front Mol Biosci. 2022-3-4

[3]
Copper induces cell death by targeting lipoylated TCA cycle proteins.

Science. 2022-3-18

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Neoplasia. 2022-3

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Cancer Discov. 2022-1

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Copper depletion modulates mitochondrial oxidative phosphorylation to impair triple negative breast cancer metastasis.

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Nat Rev Drug Discov. 2022-2

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Connecting copper and cancer: from transition metal signalling to metalloplasia.

Nat Rev Cancer. 2022-2

[10]
FDX1 can Impact the Prognosis and Mediate the Metabolism of Lung Adenocarcinoma.

Front Pharmacol. 2021-10-8

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