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Integrated analyses reveal the prognostic, immunological features and mechanisms of cuproptosis critical mediator gene FDX1 in KIRC

Genes & Immunity volume 24, pages 171–182 (2023)Cite this article

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Abstract

The ferredoxin 1 (FDX1) gene had been recently reported as a critical mediator of cuproptosis, and without doubt, its roles in KIRC would be of importance. Hence, this paper was to explore the roles of FDX1 in kidney renal clear cell carcinoma (KIRC) and its potential molecular mechanisms via scRNA-sequencing and bulk RNA-sequencing analyses. FDX1 was lowly expressed in KIRC and validated both at the protein and mRNA levels (all p < 0.05). Moreover, its elevated expression was linked with a better overall survival (OS) prognosis in KIRC (p < 0.01). The independent impact of FDX1 on KIRC prognosis was demonstrated by univariate/multivariate regression analysis (p < 0.01). Gene set enrichment analysis (GSEA) identified seven pathways strongly associated with FDX1 in KIRC. Furthermore, FDX1 was also revealed to be significantly related with immunity (p < 0.05). In addition, patients with low expression of FDX1 might be more sensitive to immunotherapies. ScRNA-seq analysis found that FDX1 could be expressed in immune cells and was mainly differently expressed in Mono/Macro cells. Ultimately, we also identified several LncRNA/RBP/FDX1 mRNA networks to reveal its underlying mechanisms in KIRC. Taken together, FDX1 was closely related to prognosis and immunity in KIRC, and its RBP-involved mechanisms of LncRNA/RBP/FDX1 networks were also revealed by us.

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Fig. 1: The mRNA expression levels of FDX1 in KIRC.
Fig. 2: Single-cell expression levels of FDX1 in the GSE159115 KIRC dataset.
Fig. 3: Relationships between FDX1 and clinicopathologic factors in the TCGA-KIRC dataset.
Fig. 4: Construction of nomogram based on FDX1 and clinicopathologic factors in the TCGA-KIRC dataset.
Fig. 5: FDX1 related pathways in KIRC by gene set enrichment analysis.
Fig. 6: Relationships between FDX1 and HRD, TMB, MSI and TNB by pan-cancer analysis.
Fig. 7: Correlations between FDX1 and immune cells infiltration, tumor microenvironment in the TCGA-KIRC dataset.
Fig. 8: Relationships between FDX1 and immune checkpoint molecules, immune cell pathways by pan-cancer analysis and scRNA-seq analysis of FDX1 expression in different KIRC GEO datasets.
Fig. 9: Prediction of immunotherapy responses.
Fig. 10: Prediction of FDX1 related mechanism in KIRC by starBase v2.0 database.

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Funding

This article was funded by the Science and Technology Project of Nantong City: JC2021183.

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  1. These authors contributed equally: Yi Wang, Xinyu Zhang, Guihua Chen.

Authors and Affiliations

  1. Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China

    Yi Wang, Guihua Chen & Xiang Wang

  2. Department of Urology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China

    Yi Wang, Xinyu Zhang & Qianwei Xing

  3. Department of Urology, Affiliated Nantong Hospital of Shanghai University (The Sixth People’s Hospital of Nantong), Nantong, 226001, Jiangsu Province, China

    Bingye Zhu

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YW & GHC: manuscript writing/editing/revising; YW & QWX: data collection or management; YW & XYZ: data analysis; BYZ & XW: protocol/project development. All the co-authors agreed to publish the final version of this manuscript.

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Correspondence to Bingye Zhu or Xiang Wang.

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Wang, Y., Zhang, X., Chen, G. et al. Integrated analyses reveal the prognostic, immunological features and mechanisms of cuproptosis critical mediator gene FDX1 in KIRC. Genes Immun 24, 171–182 (2023). https://doi.org/10.1038/s41435-023-00211-0

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