Copper Death Inducer, FDX1, as a Prognostic Biomarker Reshaping Tumor Immunity in Clear Cell Renal Cell Carcinoma
Background: Progress in the diagnosis and treatment of clear cell renal cell carcinoma (ccRCC) has significantly prolonged patient survival. However, ccRCC displays an extreme heterogenous characteristic and metastatic tendency, which limit the benefit of targeted or immune therapy. Thus, identifyin...
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MDPI AG
2023-01-01
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| Online Access: | https://www.mdpi.com/2073-4409/12/3/349 |
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| author | Aimin Jiang Juelan Ye Ye Zhou Baohua Zhu Juan Lu Silun Ge Le Qu Jianru Xiao Linhui Wang Chen Cai |
| author_facet | Aimin Jiang Juelan Ye Ye Zhou Baohua Zhu Juan Lu Silun Ge Le Qu Jianru Xiao Linhui Wang Chen Cai |
| author_sort | Aimin Jiang |
| collection | DOAJ |
| description | Background: Progress in the diagnosis and treatment of clear cell renal cell carcinoma (ccRCC) has significantly prolonged patient survival. However, ccRCC displays an extreme heterogenous characteristic and metastatic tendency, which limit the benefit of targeted or immune therapy. Thus, identifying novel biomarkers and therapeutic targets for ccRCC is of great importance. Method: Pan cancer datasets, including the expression profile, DNA methylation, copy number variation, and single nucleic variation, were introduced to decode the aberrance of copper death regulators (CDRs). Then, FDX1 was systematically analyzed in ccRCC to evaluate its impact on clinical characteristics, prognosis, biological function, immune infiltration, and therapy response. Finally, in vivo experiments were utilized to decipher FDX1 in ccRCC malignancy and its role in tumor immunity. Result: Copper death regulators were identified at the pancancer level, especially in ccRCC. FDX1 played a protective role in ccRCC, and its expression level was significantly decreased in tumor tissues, which might be regulated via CNV events. At the molecular mechanism level, FDX1 positively regulated fatty acid metabolism and oxidative phosphorylation. In addition, FDX1 overexpression restrained ccRCC cell line malignancy and enhanced tumor immunity by increasing the secretion levels of IL2 and TNFγ. Conclusions: Our research illustrated the role of FDX1 in ccRCC patients’ clinical outcomes and its impact on tumor immunity, which could be treated as a promising target for ccRCC patients. |
| first_indexed | 2024-03-11T09:50:07Z |
| format | Article |
| id | doaj.art-648230e71c7a4ffeb6128471f19a5be0 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T09:50:07Z |
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| spelling | doaj.art-648230e71c7a4ffeb6128471f19a5be02023-11-16T16:20:22ZengMDPI AGCells2073-44092023-01-0112334910.3390/cells12030349Copper Death Inducer, FDX1, as a Prognostic Biomarker Reshaping Tumor Immunity in Clear Cell Renal Cell CarcinomaAimin Jiang0Juelan Ye1Ye Zhou2Baohua Zhu3Juan Lu4Silun Ge5Le Qu6Jianru Xiao7Linhui Wang8Chen Cai9Department of Urology, Changhai Hospital Affiliated to Naval Medical University (Second Military Medical University), Shanghai 200433, ChinaWuxi School of Medicine, Jiangnan University, Wuxi 214122, ChinaDepartment of Urology, Changhai Hospital Affiliated to Naval Medical University (Second Military Medical University), Shanghai 200433, ChinaDepartment of Urology, Changhai Hospital Affiliated to Naval Medical University (Second Military Medical University), Shanghai 200433, ChinaVocational Education Center, Naval Medical University (Second Military Medical University), Shanghai 200433, ChinaDepartment of Urology, Jinling Hospital Affiliated to Medical School of Nanjing University, Nanjing 210093, ChinaDepartment of Urology, Jinling Hospital Affiliated to Medical School of Nanjing University, Nanjing 210093, ChinaWuxi School of Medicine, Jiangnan University, Wuxi 214122, ChinaDepartment of Urology, Changhai Hospital Affiliated to Naval Medical University (Second Military Medical University), Shanghai 200433, ChinaDepartment of Special Clinic, Changhai Hospital Affiliated to Naval Medical University (Second Military Medical University), Shanghai 200433, ChinaBackground: Progress in the diagnosis and treatment of clear cell renal cell carcinoma (ccRCC) has significantly prolonged patient survival. However, ccRCC displays an extreme heterogenous characteristic and metastatic tendency, which limit the benefit of targeted or immune therapy. Thus, identifying novel biomarkers and therapeutic targets for ccRCC is of great importance. Method: Pan cancer datasets, including the expression profile, DNA methylation, copy number variation, and single nucleic variation, were introduced to decode the aberrance of copper death regulators (CDRs). Then, FDX1 was systematically analyzed in ccRCC to evaluate its impact on clinical characteristics, prognosis, biological function, immune infiltration, and therapy response. Finally, in vivo experiments were utilized to decipher FDX1 in ccRCC malignancy and its role in tumor immunity. Result: Copper death regulators were identified at the pancancer level, especially in ccRCC. FDX1 played a protective role in ccRCC, and its expression level was significantly decreased in tumor tissues, which might be regulated via CNV events. At the molecular mechanism level, FDX1 positively regulated fatty acid metabolism and oxidative phosphorylation. In addition, FDX1 overexpression restrained ccRCC cell line malignancy and enhanced tumor immunity by increasing the secretion levels of IL2 and TNFγ. Conclusions: Our research illustrated the role of FDX1 in ccRCC patients’ clinical outcomes and its impact on tumor immunity, which could be treated as a promising target for ccRCC patients.https://www.mdpi.com/2073-4409/12/3/349copper death regulatorsFDX1tumor immunitymultiomicsrenal cancer |
| spellingShingle | Aimin Jiang Juelan Ye Ye Zhou Baohua Zhu Juan Lu Silun Ge Le Qu Jianru Xiao Linhui Wang Chen Cai Copper Death Inducer, FDX1, as a Prognostic Biomarker Reshaping Tumor Immunity in Clear Cell Renal Cell Carcinoma Cells copper death regulators FDX1 tumor immunity multiomics renal cancer |
| title | Copper Death Inducer, FDX1, as a Prognostic Biomarker Reshaping Tumor Immunity in Clear Cell Renal Cell Carcinoma |
| title_full | Copper Death Inducer, FDX1, as a Prognostic Biomarker Reshaping Tumor Immunity in Clear Cell Renal Cell Carcinoma |
| title_fullStr | Copper Death Inducer, FDX1, as a Prognostic Biomarker Reshaping Tumor Immunity in Clear Cell Renal Cell Carcinoma |
| title_full_unstemmed | Copper Death Inducer, FDX1, as a Prognostic Biomarker Reshaping Tumor Immunity in Clear Cell Renal Cell Carcinoma |
| title_short | Copper Death Inducer, FDX1, as a Prognostic Biomarker Reshaping Tumor Immunity in Clear Cell Renal Cell Carcinoma |
| title_sort | copper death inducer fdx1 as a prognostic biomarker reshaping tumor immunity in clear cell renal cell carcinoma |
| topic | copper death regulators FDX1 tumor immunity multiomics renal cancer |
| url | https://www.mdpi.com/2073-4409/12/3/349 |
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