{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:37:12Z","timestamp":1787027832899,"version":"build-2736575974"},"reference-count":69,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T00:00:00Z","timestamp":1673913600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81902560"],"award-info":[{"award-number":["81902560"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81730073"],"award-info":[{"award-number":["81730073"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81872074"],"award-info":[{"award-number":["81872074"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2018YFA0108300"],"award-info":[{"award-number":["2018YFA0108300"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Key Research and Development Program Stem Cell and Translational Research Key Projects","award":["81902560"],"award-info":[{"award-number":["81902560"]}]},{"name":"National Key Research and Development Program Stem Cell and Translational Research Key Projects","award":["81730073"],"award-info":[{"award-number":["81730073"]}]},{"name":"National Key Research and Development Program Stem Cell and Translational Research Key Projects","award":["81872074"],"award-info":[{"award-number":["81872074"]}]},{"name":"National Key Research and Development Program Stem Cell and Translational Research Key Projects","award":["2018YFA0108300"],"award-info":[{"award-number":["2018YFA0108300"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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 TNF\u03b3. Conclusions: Our research illustrated the role of FDX1 in ccRCC patients\u2019 clinical outcomes and its impact on tumor immunity, which could be treated as a promising target for ccRCC patients.<\/jats:p>","DOI":"10.3390\/cells12030349","type":"journal-article","created":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T06:25:46Z","timestamp":1673936746000},"page":"349","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Copper Death Inducer, FDX1, as a Prognostic Biomarker Reshaping Tumor Immunity in Clear Cell Renal Cell Carcinoma"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9563-983X","authenticated-orcid":false,"given":"Aimin","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Urology, Changhai Hospital Affiliated to Naval Medical University (Second Military Medical University), Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juelan","family":"Ye","sequence":"additional","affiliation":[{"name":"Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China"},{"name":"Department of Orthopedic, Changzheng Hospital Affiliated to Naval Medical University (Second Military Medical University), Shanghai 200003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Urology, Changhai Hospital Affiliated to Naval Medical University (Second Military Medical University), Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baohua","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Urology, Changhai Hospital Affiliated to Naval Medical University (Second Military Medical University), Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Lu","sequence":"additional","affiliation":[{"name":"Vocational Education Center, Naval Medical University (Second Military Medical University), Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silun","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Urology, Jinling Hospital Affiliated to Medical School of Nanjing University, Nanjing 210093, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Urology, Jinling Hospital Affiliated to Medical School of Nanjing University, Nanjing 210093, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianru","family":"Xiao","sequence":"additional","affiliation":[{"name":"Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China"},{"name":"Department of Orthopedic, Changzheng Hospital Affiliated to Naval Medical University (Second Military Medical University), Shanghai 200003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linhui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology, Changhai Hospital Affiliated to Naval Medical University (Second Military Medical University), Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Special Clinic, Changhai Hospital Affiliated to Naval Medical University (Second Military Medical University), Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21551","article-title":"Cancer statistics, 2019","volume":"69","author":"Siegel","year":"2019","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21590","article-title":"Cancer statistics, 2020","volume":"70","author":"Siegel","year":"2020","journal-title":"CA Cancer J. Clin."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21654","article-title":"Cancer Statistics, 2021","volume":"71","author":"Siegel","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21708","article-title":"Cancer statistics, 2022","volume":"72","author":"Siegel","year":"2022","journal-title":"CA Cancer J. Clin."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/s13058-016-0712-6","article-title":"Cancer stem cell metabolism","volume":"18","author":"Pestell","year":"2016","journal-title":"Breast Cancer Res. BCR"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"117","DOI":"10.5483\/BMBRep.2017.50.3.222","article-title":"Cancer stem cell heterogeneity: Origin and new perspectives on CSC targeting","volume":"50","author":"Eun","year":"2017","journal-title":"BMB Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1056\/NEJMoa1113205","article-title":"Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing","volume":"366","author":"Gerlinger","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1016\/S0140-6736(15)00046-X","article-title":"Renal cancer","volume":"387","author":"Capitanio","year":"2016","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"804","DOI":"10.6004\/jnccn.2017.0100","article-title":"Kidney Cancer, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology","volume":"15","author":"Motzer","year":"2017","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/s41585-020-0282-3","article-title":"Checkpoint inhibitor immunotherapy in kidney cancer","volume":"17","author":"Xu","year":"2020","journal-title":"Nat. Rev. Urol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.ucl.2020.07.009","article-title":"Kidney Cancer: An Overview of Current Therapeutic Approaches","volume":"47","author":"Chowdhury","year":"2020","journal-title":"Urol. Clin. N. Am."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2262","DOI":"10.1002\/cncr.24232","article-title":"Treatment of kidney cancer: Insights provided by the VHL tumor-suppressor protein","volume":"115","author":"Kaelin","year":"2009","journal-title":"Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1126\/science.abf0529","article-title":"Copper induces cell death by targeting lipoylated TCA cycle proteins","volume":"375","author":"Tsvetkov","year":"2022","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"11775","DOI":"10.1073\/pnas.1004250107","article-title":"Humans possess two mitochondrial ferredoxins, Fdx1 and Fdx2, with distinct roles in steroidogenesis, heme, and Fe\/S cluster biosynthesis","volume":"107","author":"Sheftel","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Wang, Z., Dong, H., Yang, L., Yi, P., Wang, Q., and Huang, D. (2021). The role of FDX1 in granulosa cell of Polycystic ovary syndrome (PCOS). BMC Endocr. Disord., 21.","DOI":"10.1186\/s12902-021-00775-w"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1038\/s41589-019-0291-9","article-title":"Mitochondrial metabolism promotes adaptation to proteotoxic stress","volume":"15","author":"Tsvetkov","year":"2019","journal-title":"Nat. Chem. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/ng.2699","article-title":"Integrated molecular analysis of clear-cell renal cell carcinoma","volume":"45","author":"Sato","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.ccell.2021.02.013","article-title":"Progressive immune dysfunction with advancing disease stage in renal cell carcinoma","volume":"39","author":"Braun","year":"2021","journal-title":"Cancer Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: An R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"Omics J. Integr. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e108","DOI":"10.1158\/0008-5472.CAN-17-0307","article-title":"TIMER: A Web Server for Comprehensive Analysis of Tumor-Infiltrating Immune Cells","volume":"77","author":"Li","year":"2017","journal-title":"Cancer Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/978-1-4939-7493-1_12","article-title":"Profiling Tumor Infiltrating Immune Cells with CIBERSORT","volume":"1711","author":"Chen","year":"2018","journal-title":"Methods Mol. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1186\/s13059-017-1349-1","article-title":"xCell: Digitally portraying the tissue cellular heterogeneity landscape","volume":"18","author":"Aran","year":"2017","journal-title":"Genome Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/978-1-0716-0327-7_17","article-title":"EPIC: A Tool to Estimate the Proportions of Different Cell Types from Bulk Gene Expression Data","volume":"2120","author":"Racle","year":"2020","journal-title":"Methods Mol. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1038\/s41591-018-0136-1","article-title":"Signatures of T cell dysfunction and exclusion predict cancer immunotherapy response","volume":"24","author":"Jiang","year":"2018","journal-title":"Nat. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1093\/bioinformatics\/btx744","article-title":"GDSCTools for mining pharmacogenomic interactions in cancer","volume":"34","author":"Cokelaer","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1101\/gr.239244.118","article-title":"Maftools: Efficient and comprehensive analysis of somatic variants in cancer","volume":"28","author":"Mayakonda","year":"2018","journal-title":"Genome Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"R41","DOI":"10.1186\/gb-2011-12-4-r41","article-title":"GISTIC2.0 facilitates sensitive and confident localization of the targets of focal somatic copy-number alteration in human cancers","volume":"12","author":"Mermel","year":"2011","journal-title":"Genome Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e5910575","DOI":"10.1155\/2022\/5910575","article-title":"CCNA2 as an Immunological Biomarker Encompassing Tumor Microenvironment and Therapeutic Response in Multiple Cancer Types","volume":"2022","author":"Jiang","year":"2022","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3158","DOI":"10.7150\/ijbs.62553","article-title":"DDX39 as a predictor of clinical prognosis and immune checkpoint therapy efficacy in patients with clear cell renal cell carcinoma","volume":"17","author":"Bao","year":"2021","journal-title":"Int. J. Biol. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6665974","DOI":"10.1155\/2020\/6665974","article-title":"EGFR-AS1 Promotes Bladder Cancer Progression by Upregulating EGFR","volume":"2020","author":"Wang","year":"2020","journal-title":"BioMed Res. Int."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"842069","DOI":"10.3389\/fimmu.2022.842069","article-title":"Elevated SNRPA1, as a Promising Predictor Reflecting Severe Clinical Outcome via Effecting Tumor Immunity for ccRCC, Is Related to Cell Invasion, Metastasis, and Sunitinib Sensitivity","volume":"13","author":"Jiang","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.celrep.2018.03.075","article-title":"The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma","volume":"23","author":"Ricketts","year":"2018","journal-title":"Cell Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1016\/j.cell.2017.04.016","article-title":"An Immune Atlas of Clear Cell Renal Cell Carcinoma","volume":"169","author":"Chevrier","year":"2017","journal-title":"Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1038\/s41581-020-0316-3","article-title":"The immunology of renal cell carcinoma","volume":"16","author":"Rini","year":"2020","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Deleuze, A., Saout, J., Dugay, F., Peyronnet, B., Mathieu, R., Verhoest, G., Bensalah, K., Crouzet, L., Laguerre, B., and Belaud-Rotureau, M.-A. (2020). Immunotherapy in Renal Cell Carcinoma: The Future Is Now. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072532"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1158\/2326-6066.CIR-16-0072","article-title":"The Intratumoral Balance between Metabolic and Immunologic Gene Expression Is Associated with Anti-PD-1 Response in Patients with Renal Cell Carcinoma","volume":"4","author":"Ascierto","year":"2016","journal-title":"Cancer Immunol. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1038\/s42003-020-01625-6","article-title":"Mapping the immune environment in clear cell renal carcinoma by single-cell genomics","volume":"4","author":"Borcherding","year":"2021","journal-title":"Commun. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2476","DOI":"10.1016\/j.celrep.2016.02.024","article-title":"Multilevel Genomics-Based Taxonomy of Renal Cell Carcinoma","volume":"14","author":"Chen","year":"2016","journal-title":"Cell Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1056\/NEJMoa1712126","article-title":"Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma","volume":"378","author":"Motzer","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1056\/NEJMoa1510665","article-title":"Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma","volume":"373","author":"Motzer","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6384","DOI":"10.1002\/cam4.4190","article-title":"PD-1\/PD-L1 inhibitors-based treatment for advanced renal cell carcinoma: Mechanisms affecting efficacy and combination therapies","volume":"10","author":"Ding","year":"2021","journal-title":"Cancer Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1016\/j.eururo.2017.02.010","article-title":"CheckMate 025 Randomized Phase 3 Study: Outcomes by Key Baseline Factors and Prior Therapy for Nivolumab Versus Everolimus in Advanced Renal Cell Carcinoma","volume":"72","author":"Escudier","year":"2017","journal-title":"Eur. Urol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Zarrabi, K.K., Lanade, O., and Geynisman, D.M. (2022). Determining Front-Line Therapeutic Strategy for Metastatic Clear Cell Renal Cell Carcinoma. Cancers, 14.","DOI":"10.3390\/cancers14194607"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Chen, Y.-W., Rini, B.I., and Beckermann, K.E. (2022). Emerging Targets in Clear Cell Renal Cell Carcinoma. Cancers, 14.","DOI":"10.3390\/cancers14194843"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1016\/j.it.2021.10.003","article-title":"Unleashing TNF cytotoxicity to enhance cancer immunotherapy","volume":"42","author":"Freeman","year":"2021","journal-title":"Trends Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1158\/2159-8290.CD-20-0805","article-title":"Fueling the Fire: Inflammatory Forms of Cell Death and Implications for Cancer Immunotherapy","volume":"11","author":"Rosenbaum","year":"2021","journal-title":"Cancer Discov."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/j.molmed.2018.05.004","article-title":"Beyond Cell Death: New Functions for TNF Family Cytokines in Autoimmunity and Tumor Immunotherapy","volume":"24","author":"Yi","year":"2018","journal-title":"Trends Mol. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e2006231","DOI":"10.1002\/smll.202006231","article-title":"Copper-Based Nanoscale Coordination Polymers Augmented Tumor Radioimmunotherapy for Immunogenic Cell Death Induction and T-Cell Infiltration","volume":"17","author":"Wang","year":"2021","journal-title":"Small"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1038\/nature13180","article-title":"Copper is required for oncogenic BRAF signalling and tumorigenesis","volume":"509","author":"Brady","year":"2014","journal-title":"Nature"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"927028","DOI":"10.3389\/fonc.2022.927028","article-title":"A novel defined cuproptosis-related gene signature for predicting the prognosis of colon adenocarcinoma","volume":"12","author":"Luo","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"930041","DOI":"10.3389\/fphar.2022.930041","article-title":"Comprehensive Analysis of Cuproptosis-Related Genes in Immune Infiltration and Prognosis in Melanoma","volume":"13","author":"Lv","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1065701","DOI":"10.3389\/fphar.2022.1065701","article-title":"Comprehensive analysis of cuproptosis-related lncRNAs model in tumor immune microenvironment and prognostic value of cervical cancer","volume":"13","author":"Wang","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1186\/s12967-022-03630-1","article-title":"System analysis based on the cuproptosis-related genes identifies LIPT1 as a novel therapy target for liver hepatocellular carcinoma","volume":"20","author":"Yan","year":"2022","journal-title":"J. Transl. Med."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Tang, X., Guo, T., Wu, X., Gan, X., Wang, Y., Jia, F., Zhang, Y., Xing, X., Gao, X., and Li, Z. (2022). Clinical Significance and Immune Infiltration Analyses of the Cuproptosis-Related Human Copper Proteome in Gastric Cancer. Biomolecules, 12.","DOI":"10.3390\/biom12101459"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"954653","DOI":"10.3389\/fimmu.2022.954653","article-title":"A novel cuproptosis-related prognostic lncRNA signature for predicting immune and drug therapy response in hepatocellular carcinoma","volume":"13","author":"Chen","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"427","DOI":"10.21037\/atm.2019.08.113","article-title":"Genome-wide mutation profiling and related risk signature for prognosis of papillary renal cell carcinoma","volume":"7","author":"Zhang","year":"2019","journal-title":"Ann. Transl. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1111\/cge.12265","article-title":"Broadening the phenotype of LRP2 mutations: A new mutation in LRP2 causes a predominantly ocular phenotype suggestive of Stickler syndrome","volume":"86","author":"Schrauwen","year":"2014","journal-title":"Clin. Genet."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1016\/j.cell.2011.10.033","article-title":"Programmed Cell Death in Animal Development and Disease","volume":"147","author":"Fuchs","year":"2011","journal-title":"Cell"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Li, Z., Duan, Z., Jia, K., Yao, Y., Liu, K., Qiao, Y., Gao, Q., Yang, Y., Li, G., and Shang, A. (2022). A Combined Risk Score Model to Assess Prognostic Value in Patients with Soft Tissue Sarcomas. Cells, 11.","DOI":"10.3390\/cells11244077"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Ma, W., Zhu, L., Song, S., Liu, B., and Gu, J. (2022). Identification and Validation of Glycosyltransferases Correlated with Cuproptosis as a Prognostic Model for Colon Adenocarcinoma. Cells, 11.","DOI":"10.3390\/cells11233728"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"939956","DOI":"10.3389\/fgene.2022.939956","article-title":"A comprehensive analysis and validation of cuproptosis-associated genes across cancers: Overall survival, the tumor microenvironment, stemness scores, and drug sensitivity","volume":"13","author":"Liu","year":"2022","journal-title":"Front. Genet."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1186\/s12957-022-02727-7","article-title":"Cuproptosis-related lncRNA predict prognosis and immune response of lung adenocarcinoma","volume":"20","author":"Wang","year":"2022","journal-title":"World J. Surg. Oncol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1186\/s13045-022-01392-3","article-title":"Targeting cell death pathways for cancer therapy: Recent developments in necroptosis, pyroptosis, ferroptosis, and cuproptosis research","volume":"15","author":"Tong","year":"2022","journal-title":"J. Hematol. Oncol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.3389\/fimmu.2018.01310","article-title":"Myeloid-Derived Suppressor Cells Hinder the Anti-Cancer Activity of Immune Checkpoint Inhibitors","volume":"9","author":"Weber","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1158\/1078-0432.CCR-20-1610","article-title":"Blocking IL1 Beta Promotes Tumor Regression and Remodeling of the Myeloid Compartment in a Renal Cell Carcinoma Model: Multidimensional Analyses","volume":"27","author":"Aggen","year":"2021","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2346","DOI":"10.1158\/1078-0432.CCR-15-1823","article-title":"Myeloid-Derived Suppressor Cell Subset Accumulation in Renal Cell Carcinoma Parenchyma Is Associated with Intratumoral Expression of IL1\u03b2, IL8, CXCL5, and Mip-1\u03b1","volume":"23","author":"Najjar","year":"2017","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"749134","DOI":"10.3389\/fphar.2021.749134","article-title":"FDX1 can Impact the Prognosis and Mediate the Metabolism of Lung Adenocarcinoma","volume":"12","author":"Zhang","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1056\/NEJMoa2035716","article-title":"CLEAR Trial Investigators. Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma","volume":"384","author":"Motzer","year":"2021","journal-title":"N. 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