Huang Xing, Wang Tao, Ye Jiali, Feng Huayi, Zhang Xiangyi, Ma Xin, Wang Baojun, Huang Yan, Zhang Xu
Senior Department of Urology, The Third Medical Centre of PLA General Hospital, Beijing, China.
Medical School of Chinese PLA, Beijing, China.
Front Genet. 2022 Sep 16;13:994741. doi: 10.3389/fgene.2022.994741. eCollection 2022.
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.
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。
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