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ORIGINAL RESEARCH article

Front. Oncol.
Sec. Genitourinary Oncology
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1409620
This article is part of the Research Topic Women in Genitourinary Oncology Vol III: 2023 View all 5 articles

The signature genes of cuproptosis associates with tumor immune microenvironment and predicts prognosis in kidney renal clear cell carcinoma

Provisionally accepted
Shuhan Liu Shuhan Liu 1Shijie Lv Shijie Lv 2*Xi Li Xi Li 1*Weiguo Lu Weiguo Lu 1*Shengjie Chen Shengjie Chen 1*
  • 1 The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
  • 2 Department of Pharmacology, School of Medicine, Jinan University, Guangzhou, China

The final, formatted version of the article will be published soon.

    Background: Cuproptosis is a new form of cell death, which has great potential to be developed in tumors treatment. Our study aimed to explore the predictive value of cuproptosis-related genes (CRGs) in various cancers, with a focus on kidney renal clear cell carcinoma (KIRC). Method: A total of 9502 pan-cancer patients from TCGA cohort were enrolled. The relationships between CRGs and overall survival (OS) or disease-free survival (DFS) were analyzed. Gene Set Variation Analysis (GSVA) enrichment analysis was performed to explore the expression differences of CRGs. Multivariate Cox regression analysis was used to evaluate the association between GSVA scores and patient survival. KEGG and GO analyses were employed to identify the biological functions and pathways. The expression and prognostic characteristics of FDX1 were examined to evaluate the correlation between FDX1 and KIRC. Cell experiments were conducted to verify whether FDX1 was involved in cuproptosis of Caki-1 cells induced by Elesclomol. Results: Positive cuproptosis signature genes(pos.cu.sig) exhibited the correlation with prognosis in KIRC, and all of these genes showed differential expression between KIRC and normal tissues. The GSVA score of pos.cu.sig was associated with excellent survival (HR=0.61, P<0.05), which can also serve as an independent prognostic factor for KIRC. There was a close correlation between pos.cu.sig and the tumor immune microenvironment in KIRC by KEGG and GO analysis. FDX1 expression was correlated with KIRC grade and positively associated with prognosis in KIRC patients. Compared with the control group, cell proliferation and migration were significantly inhibited, FDX1 expression was up-regulated, and Fe-S cluster protein content was decreased of Caki-1 cells after Elesclomol treatment. Conclusions: This study provides compelling evidence that cuproptosis is closely linked to the prognosis of KIRC. FDX1 holds promise as a viable biomarker and therapeutic target for assessing the effectiveness of tumor immunotherapy in KIRC.

    Keywords: cuproptosis, CRGs, Tumor immune microenvironment, Fdx1, KIRC

    Received: 30 Mar 2024; Accepted: 29 Jul 2024.

    Copyright: © 2024 Liu, Lv, Li, Lu and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Shijie Lv, Department of Pharmacology, School of Medicine, Jinan University, Guangzhou, 510630, China
    Xi Li, The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
    Weiguo Lu, The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
    Shengjie Chen, The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China

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