PDF(Pubmed)
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：
铁氧还蛋白1(FDX1),一种铁硫蛋白,负责一系列代谢氧化还原反应中的电子转移。透明细胞肾细胞癌（ccRCC）是一种以代谢重编程为特征的侵袭性癌症，FDX1是角化的关键调节剂。然而,与ccRCC临床病理特征相关的FDX1的表达谱和预后价值在很大程度上仍未阐明。在这项研究中,我们整合了一系列公开的生物信息学分析，以探索人类癌症和细胞系中FDX1的mRNA和蛋白质谱，并验证其表达和预后价值，尤其是在ccRCC中。在这项研究中,FDX1mRNA和蛋白表达异常下调，并与ccRCC分级相关。舞台,淋巴结转移，而在邻近的非肿瘤肾组织中，它在肾小管上皮细胞中大量表达并在细胞质中定位。多变量分析表明，低FDX1表达导致不利的整体和无病生存。ccRCC中FDX1共表达基因的功能富集主要涉及各种代谢过程中的线粒体功能障碍和生物氧化,除了铁硫簇生物生成。此外，FDX1调节免疫浸润影响预后。因此，由于ccRCC肿瘤发生，FDX1下调是机械上的，并且是对ccRCC患者进行分层的有希望的预后生物标志物。
