{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T09:19:26Z","timestamp":1783070366952,"version":"3.54.6"},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T00:00:00Z","timestamp":1778371200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":54,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004509","name":"Health and Family Planning Commission of Guangdong Province","doi-asserted-by":"crossref","award":["A2024052"],"award-info":[{"award-number":["A2024052"]}],"id":[{"id":"10.13039\/501100004509","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100013050","name":"Guangdong Provincial Applied Science and Technology Research and Development Program","doi-asserted-by":"crossref","award":["2023A1515111152"],"award-info":[{"award-number":["2023A1515111152"]}],"id":[{"id":"10.13039\/501100013050","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82503271"],"award-info":[{"award-number":["82503271"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82472904"],"award-info":[{"award-number":["82472904"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100010843","name":"Guangzhou Science, Technology and Innovation Commission","doi-asserted-by":"crossref","award":["2024MS006"],"award-info":[{"award-number":["2024MS006"]}],"id":[{"id":"10.13039\/501100010843","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Exp Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The prognostic values of cuproptosis-related genes (CRGs) in gastric cancer with lymph node metastasis (GCLM), especially in the tumor immune microenvironment (TIME), remain unclear. We analyzed the expression, mutation, immunity, drug sensitivity, and prognostic value of CRGs in GCLM using TCGA and GEO cohorts. Consensus clustering was performed to identify CRG subtypes, with differences characterized by multi-omics analysis. A CRG-based prognostic risk score and immune score were constructed for individualized assessment, and the role of CRGs was validated through in vitro and in vivo experiments. Consensus clustering revealed that CRGs were significantly enriched in biological processes related to mitosis and energy metabolism, as well as in immune-related and cancer-associated pathways. Four distinct CRG subtypes were identified, showing marked differences in expression profiles, prognosis, genetic alterations, TIME, and chemotherapeutic drug sensitivity. We developed an exploratory CRG-based prognostic risk score for preliminary individualized assessment, and the functional relevance of CRGs in GCLM was further validated through in vitro experiments. Among these, FDX1, LIAS, DLAT, MTF1, and GLS were identified as key determinants of overall survival in patients with GCLM, with FDX1 emerging as a potential independent prognostic factor. Notably, upregulation of FDX1 significantly suppressed lymph node metastasis of gastric cancer cells in a mouse popliteal lymph node metastasis model. Our data uncovers FDX1 might be a potential favorable prognostic factors in GCLM patients. These findings may improve our understanding of CRGs in GCLM and provide new in-sights for assessing prognosis and developing more effective treatment strategies.<\/jats:p>","DOI":"10.1007\/s10238-026-02160-0","type":"journal-article","created":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T04:04:17Z","timestamp":1778385857000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["FDX1 as a predictive biomarker and therapeutic target for lymph node metastasis in gastric cancer"],"prefix":"10.1007","volume":"26","author":[{"given":"Tianhao","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianqiu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zikang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixin","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhui","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meilan","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinping","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,10]]},"reference":[{"issue":"3","key":"2160_CR1","first-page":"209","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J]. CA Cancer J Clin. 2021;71(3):209\u201349.","journal-title":"CA Cancer J Clin"},{"issue":"9972","key":"2160_CR2","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1016\/S0140-6736(14)62038-9","volume":"385","author":"C Allemani","year":"2015","unstructured":"Allemani C, Weir HK, Carreira H, et al. Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2). Lancet. 2015;385(9972):977\u20131010.","journal-title":"Lancet"},{"issue":"1","key":"2160_CR3","first-page":"47","volume":"4","author":"B Han","year":"2024","unstructured":"Han B, Zheng R, Zeng H, et al. Cancer incidence and mortality in China, 2022 [J]. J Natl Cancer Cent. 2024;4(1):47\u201353.","journal-title":"J Natl Cancer Cent"},{"key":"2160_CR4","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1435651","volume":"15","author":"Y Li","year":"2024","unstructured":"Li Y, Sun W, Yuan S, et al. The role of cuproptosis in gastric cancer. Front Immunol. 2024;15:1435651.","journal-title":"Front Immunol"},{"key":"2160_CR5","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.cois.2017.07.001","volume":"23","author":"JA Dow","year":"2017","unstructured":"Dow JA. The essential roles of metal ions in insect homeostasis and physiology. Current Opinion in Insect Science. 2017;23:43\u201350.","journal-title":"Current Opinion in Insect Science"},{"issue":"6586","key":"2160_CR6","doi-asserted-by":"publisher","first-page":"1254","DOI":"10.1126\/science.abf0529","volume":"375","author":"P Tsvetkov","year":"2022","unstructured":"Tsvetkov P, Coy S, Petrova B, et al. Copper induces cell death by targeting lipoylated TCA cycle proteins [J]. Science. 2022;375(6586):1254\u201361.","journal-title":"Science"},{"issue":"7","key":"2160_CR7","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1038\/s41589-019-0291-9","volume":"15","author":"P Tsvetkov","year":"2019","unstructured":"Tsvetkov P, Detappe A, Cai K, et al. Mitochondrial metabolism promotes adaptation to proteotoxic stress. Nat Chem Biol. 2019;15(7):681\u20139.","journal-title":"Nat Chem Biol"},{"key":"2160_CR8","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.jinorgbio.2014.04.004","volume":"137","author":"BB Hasinoff","year":"2014","unstructured":"Hasinoff BB, Yadav AA, Patel D, et al. The cytotoxicity of the anticancer drug elesclomol is due to oxidative stress indirectly mediated through its complex with Cu(II). J Inorg Biochem. 2014;137:22\u201330.","journal-title":"J Inorg Biochem"},{"issue":"16","key":"2160_CR9","doi-asserted-by":"publisher","first-page":"6235","DOI":"10.1021\/ja109413c","volume":"133","author":"S Tardito","year":"2011","unstructured":"Tardito S, Bassanetti I, Bignardi C, et al. Copper binding agents acting as Copper lonophores lead to caspase inhibition and paraptotic cell death in human cancer cells. J Am Chem Soc. 2011;133(16):6235\u201342.","journal-title":"J Am Chem Soc"},{"issue":"2","key":"2160_CR10","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1038\/s43018-019-0018-6","volume":"1","author":"SM Corsello","year":"2020","unstructured":"Corsello SM, Nagari RT, Spangler RD, et al. Discovering the anti-cancer potential of non-oncology drugs by systematic viability profiling [J]. Nat Cancer. 2020;1(2):235\u201348.","journal-title":"Nat Cancer"},{"issue":"2","key":"2160_CR11","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1039\/C6MT00202A","volume":"9","author":"S Blockhuys","year":"2017","unstructured":"Blockhuys S, Celauro E, Hildesj\u00f6 C, et al. Defining the human copper proteome and analysis of its expression variation in cancers [J]. Metallomics. 2017;9(2):112\u201323.","journal-title":"Metallomics"},{"key":"2160_CR12","doi-asserted-by":"publisher","DOI":"10.1186\/1746-160X-2-33","volume":"2","author":"SS Khanna","year":"2006","unstructured":"Khanna SS, Karjodkar FR. Circulating immune complexes and trace elements (Copper, Iron and Selenium) as markers in oral precancer and cancer: a randomised, controlled clinical trial. Head Face Med. 2006;2:33.","journal-title":"Head Face Med"},{"issue":"1","key":"2160_CR13","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1007\/s12011-016-0768-2","volume":"175","author":"AK Baltaci","year":"2017","unstructured":"Baltaci AK, Dundar TK, Aksoy F, et al. Changes in the Serum Levels of Trace Elements Before and After the Operation in Thyroid Cancer Patients [J]. Biol Trace Elem Res. 2017;175(1):57\u201364.","journal-title":"Biol Trace Elem Res"},{"issue":"10","key":"2160_CR14","doi-asserted-by":"publisher","first-page":"7930","DOI":"10.1007\/s11356-014-3970-9","volume":"22","author":"X Ding","year":"2015","unstructured":"Ding X, Jiang M, Jing H, et al. Analysis of serum levels of 15 trace elements in breast cancer patients in Shandong, China [J]. Environ Sci Pollut Res Int. 2015;22(10):7930\u20135.","journal-title":"Environ Sci Pollut Res Int"},{"issue":"1","key":"2160_CR15","doi-asserted-by":"publisher","first-page":"106","DOI":"10.4103\/0019-509X.175573","volume":"52","author":"ML Adeoti","year":"2015","unstructured":"Adeoti ML, Oguntola AS, Akanni EO, et al. Trace elements; copper, zinc and selenium, in breast cancer afflicted female patients in LAUTECH Osogbo, Nigeria [J]. Indian J Cancer. 2015;52(1):106\u20139.","journal-title":"Indian J Cancer"},{"issue":"4","key":"2160_CR16","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1002\/1097-0142(19890215)63:4<726::AID-CNCR2820630421>3.0.CO;2-P","volume":"63","author":"M D\u00ecez","year":"1989","unstructured":"D\u00ecez M, Cerd\u00e0n FJ, Arroyo M, et al. Use of the copper\/zinc ratio in the diagnosis of lung cancer [J]. Cancer. 1989;63(4):726\u201330.","journal-title":"Cancer"},{"issue":"2","key":"2160_CR17","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1016\/j.canep.2010.06.004","volume":"35","author":"Y Jin","year":"2011","unstructured":"Jin Y, Zhang C, Xu H, et al. Combined effects of serum trace metals and polymorphisms of CYP1A1 or GSTM1 on non-small cell lung cancer: a hospital based case-control study in China. Cancer Epidemiol. 2011;35(2):182\u20137.","journal-title":"Cancer Epidemiol"},{"issue":"Suppl 1","key":"2160_CR18","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1590\/S0102-86502016001300006","volume":"31","author":"SM Ribeiro","year":"2016","unstructured":"Ribeiro SM, Moya AM, Braga CB, et al. Copper-Zinc ratio and nutritional status in colorectal cancer patients during the perioperative period. Acta Cir Bras. 2016;31(Suppl 1):24\u20138.","journal-title":"Acta Cir Bras"},{"issue":"4","key":"2160_CR19","doi-asserted-by":"publisher","first-page":"612","DOI":"10.3748\/wjg.v13.i4.612","volume":"13","author":"M Yaman","year":"2007","unstructured":"Yaman M, Kaya G, Yekeler H. Distribution of trace metal concentrations in paired cancerous and non-cancerous human stomach tissues. World J Gastroenterol. 2007;13(4):612\u20138.","journal-title":"World J Gastroenterol"},{"issue":"1","key":"2160_CR20","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1159\/000499261","volume":"14","author":"SAK Saleh","year":"2020","unstructured":"Saleh SAK, Adly HM, Abdelkhaliq AA, et al. Serum levels of selenium, zinc, copper, manganese, and iron in prostate cancer patients. Curr Urol. 2020;14(1):44\u20139.","journal-title":"Curr Urol"},{"issue":"11","key":"2160_CR21","doi-asserted-by":"publisher","first-page":"2641","DOI":"10.1007\/s00268-013-2164-9","volume":"37","author":"S Basu","year":"2013","unstructured":"Basu S, Singh MK, Singh TB, et al. Heavy and trace metals in carcinoma of the gallbladder [J]. World J Surg. 2013;37(11):2641\u20136.","journal-title":"World J Surg"},{"issue":"5","key":"2160_CR22","doi-asserted-by":"publisher","first-page":"868","DOI":"10.1002\/1097-0142(19830901)52:5<868::AID-CNCR2820520521>3.0.CO;2-K","volume":"52","author":"EJ Margalioth","year":"1983","unstructured":"Margalioth EJ, Schenker JG, Chevion M. Copper and zinc levels in normal and malignant tissues. Cancer. 1983;52(5):868\u201372.","journal-title":"Cancer"},{"issue":"48","key":"2160_CR23","doi-asserted-by":"publisher","first-page":"19507","DOI":"10.1073\/pnas.1318431110","volume":"110","author":"S Ishida","year":"2013","unstructured":"Ishida S, Andreux P, Poitry-Yamate C, et al. Bioavailable copper modulates oxidative phosphorylation and growth of tumors. Proc Natl Acad Sci U S A. 2013;110(48):19507\u201312.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"2160_CR24","doi-asserted-by":"publisher","first-page":"2076","DOI":"10.1073\/pnas.1914267117","volume":"117","author":"CR Wooton-Kee","year":"2020","unstructured":"Wooton-Kee CR, Robertson M, Zhou Y, et al. Metabolic dysregulation in the Atp7b (-\/-) Wilson\u2019s disease mouse model. Proc Natl Acad Sci U S A. 2020;117(4):2076\u201383.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"9","key":"2160_CR25","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.2006519","volume":"16","author":"H Yang","year":"2018","unstructured":"Yang H, Ralle M, Wolfgang MJ, et al. Copper-dependent amino oxidase 3 governs selection of metabolic fuels in adipocytes. PLoS Biol. 2018;16(9):e2006519.","journal-title":"PLoS Biol"},{"issue":"4","key":"2160_CR26","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1038\/s41556-020-0481-4","volume":"22","author":"T Tsang","year":"2020","unstructured":"Tsang T, Posimo JM, Gudiel AA, et al. Copper is an essential regulator of the autophagic kinases ULK1\/2 to drive lung adenocarcinoma. Nat Cell Biol. 2020;22(4):412\u201324.","journal-title":"Nat Cell Biol"},{"issue":"W1","key":"2160_CR27","doi-asserted-by":"publisher","first-page":"W98","DOI":"10.1093\/nar\/gkx247","volume":"45","author":"Z Tang","year":"2017","unstructured":"Tang Z, Li C, Kang B, et al. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017;45(W1):W98\u2013102.","journal-title":"Nucleic Acids Res"},{"issue":"8","key":"2160_CR28","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1016\/j.neo.2017.05.002","volume":"19","author":"DS Chandrashekar","year":"2017","unstructured":"Chandrashekar DS, Bashel B, Balasubramanya SAH, et al. UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses [J]. Neoplasia. 2017;19(8):649\u201358.","journal-title":"Neoplasia"},{"issue":"6220","key":"2160_CR29","doi-asserted-by":"publisher","first-page":"1260419","DOI":"10.1126\/science.1260419","volume":"347","author":"M Uhlen","year":"2015","unstructured":"Uhlen M, Fagerberg L, Hallstrom BM, et al. Proteomics. tissue-based map of the human proteome [J]. Sci. 2015;347(6220):1260419.","journal-title":"Sci"},{"issue":"1","key":"2160_CR30","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-27521-y","volume":"8","author":"A Nagy","year":"2018","unstructured":"Nagy A, Lanczky A, Menyhart O, et al. Validation of miRNA prognostic power in hepatocellular carcinoma using expression data of independent datasets. Sci Rep. 2018;8(1):9227.","journal-title":"Sci Rep"},{"issue":"7","key":"2160_CR31","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007","volume":"43","author":"ME Ritchie","year":"2015","unstructured":"Ritchie ME, Phipson B, Wu D, et al. Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43(7):e47.","journal-title":"Nucleic Acids Res"},{"issue":"5","key":"2160_CR32","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","volume":"16","author":"G Yu","year":"2012","unstructured":"Yu G, Wang LG, Han Y, et al. clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS. 2012;16(5):284\u20137.","journal-title":"OMICS"},{"issue":"5","key":"2160_CR33","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1158\/2159-8290.CD-12-0095","volume":"2","author":"E Cerami","year":"2012","unstructured":"Cerami E, Gao J, Dogrusoz U, et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2012;2(5):401\u20134.","journal-title":"Cancer Discov"},{"issue":"269","key":"2160_CR34","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2004088","volume":"6","author":"J Gao","year":"2013","unstructured":"Gao J, Aksoy BA, Dogrusoz U, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. 2013;6(269):pl1.","journal-title":"Sci Signal"},{"issue":"1","key":"2160_CR35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v033.i01","volume":"33","author":"J Friedman","year":"2010","unstructured":"Friedman J, Hastie T, Tibshirani R. Regularization paths for generalized linear models via coordinate descent. J Stat Softw. 2010;33(1):1\u201322.","journal-title":"J Stat Softw"},{"key":"2160_CR36","doi-asserted-by":"publisher","first-page":"719613","DOI":"10.3389\/fcell.2021.719613","volume":"9","author":"TH Zhang","year":"2021","unstructured":"Zhang TH, Lai SR, Cai YZ, et al. Comprehensive Analysis and Identification of Prognostic Biomarkers and Therapeutic Targets Among FAM83 Family Members for Gastric Cancer [J]. Frontiers in Cell and Developmental Biol. 2021;9:719613.","journal-title":"Frontiers in Cell and Developmental Biol"},{"issue":"1","key":"2160_CR37","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.ejso.2019.09.143","volume":"46","author":"SH Jeong","year":"2020","unstructured":"Jeong SH, Kim RB, Park SY, et al. Nomogram for predicting gastric cancer recurrence using biomarker gene expression. Eur J Surg Oncol. 2020;46(1):195\u2013201.","journal-title":"Eur J Surg Oncol"},{"issue":"21","key":"2160_CR38","doi-asserted-by":"publisher","first-page":"e108","DOI":"10.1158\/0008-5472.CAN-17-0307","volume":"77","author":"T Li","year":"2017","unstructured":"Li T, Fan J, Wang B, et al. TIMER: A Web Server for Comprehensive Analysis of Tumor-Infiltrating Immune Cells [J]. Cancer Res. 2017;77(21):e108\u201310.","journal-title":"Cancer Res"},{"issue":"4","key":"2160_CR39","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1002\/cac2.12281","volume":"42","author":"Y Liu","year":"2022","unstructured":"Liu Y, Zhai E, Chen J, et al. m(6) A-mediated regulation of PBX1-GCH1 axis promotes gastric cancer proliferation and metastasis by elevating tetrahydrobiopterin levels. Cancer Commun. 2022;42(4):327\u201344.","journal-title":"Cancer Commun"},{"issue":"9","key":"2160_CR40","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1038\/s41568-020-0273-y","volume":"20","author":"RD Leone","year":"2020","unstructured":"Leone RD, Powell JD. Metabolism of immune cells in cancer. Nat Rev Cancer. 2020;20(9):516\u201331.","journal-title":"Nat Rev Cancer"},{"key":"2160_CR41","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.938134","volume":"13","author":"L Yang","year":"2022","unstructured":"Yang L, Zhang Y, Wang Y, et al. Ferredoxin 1 is a cuproptosis-key gene responsible for tumor immunity and drug sensitivity: A pan-cancer analysis [J]. Front Pharmacol. 2022;13:938134.","journal-title":"Front Pharmacol"},{"issue":"Pt 1","key":"2160_CR42","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2025.147996","volume":"330","author":"A Wu","year":"2025","unstructured":"Wu A, Tu K, Xia G. The emerging role of ferredoxin 1 in cancer: insights into cuproptosis and therapeutic innovation. Int J Biol Macromol. 2025;330(Pt 1):147996.","journal-title":"Int J Biol Macromol"},{"key":"2160_CR43","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1265565","volume":"14","author":"F Xu","year":"2023","unstructured":"Xu F, Cai D, Yang Z, et al. Commentary: copper and cuproptosis-related genes in hepatocellular carcinoma: therapeutic biomarkers targeting tumor immune microenvironment and immune checkpoints. Front Immunol. 2023;14:1265565.","journal-title":"Front Immunol"},{"issue":"7418","key":"2160_CR44","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1038\/nature11412","volume":"490","author":"CANCER GENOME ATLAS N","year":"2012","unstructured":"CANCER GENOME ATLAS N. Comprehensive molecular portraits of human breast tumours. Nat. 2012;490(7418):61\u201370.","journal-title":"Nat"},{"issue":"2","key":"2160_CR45","doi-asserted-by":"publisher","first-page":"251","DOI":"10.17305\/bb.2025.12751","volume":"26","author":"XH Song","year":"2025","unstructured":"Song XH, Ding YH, Chen JS. Tumor glucose reprogramming suppresses cuproptosis: a review. Biomol Biomed. 2025;26(2):251\u201361.","journal-title":"Biomol Biomed"},{"key":"2160_CR46","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103302","volume":"75","author":"B Sun","year":"2024","unstructured":"Sun B, Ding P, Song Y, et al. FDX1 downregulation activates mitophagy and the PI3K\/AKT signaling pathway to promote hepatocellular carcinoma progression by inducing ROS production [J]. Redox Biol. 2024;75:103302.","journal-title":"Redox Biol"},{"key":"2160_CR47","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1016\/j.freeradbiomed.2025.12.019","volume":"244","author":"Y Lu","year":"2026","unstructured":"Lu Y, Li Y, Sun X, et al. Mitochondrial uncoupling sensitizes gastric cancer cells to elesclomol-induced cuproptosis via FDX1\/DLAT upregulation. Free Radic Biol Med. 2026;244:284\u201395.","journal-title":"Free Radic Biol Med"},{"key":"2160_CR48","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12113380","author":"AG Solimando","year":"2020","unstructured":"Solimando AG, Summa S, Vacca A, et al. Cancer-associated angiogenesis: the endothelial cell as a checkpoint for immunological patrolling. Cancers (Basel). 2020. https:\/\/doi.org\/10.3390\/cancers12113380.","journal-title":"Cancers (Basel)"}],"container-title":["Clinical and Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10238-026-02160-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10238-026-02160-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10238-026-02160-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T08:46:54Z","timestamp":1783068414000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10238-026-02160-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,10]]},"references-count":48,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["2160"],"URL":"https:\/\/doi.org\/10.1007\/s10238-026-02160-0","relation":{},"ISSN":["1591-9528"],"issn-type":[{"value":"1591-9528","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,10]]},"assertion":[{"value":"26 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was admitted by the Institutional Review Board of The First Affiliated Hospital, Sun Yat-sen University. The animal study was carried out in compliance with the guidance suggestion of Animal Care Committee of the First Affiliated Hospital of Sun Yat-sen University (permit number: [2021] 737).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"The studies involving human participants were reviewed and approved by the First Affiliated Hospital of Sun Yat-sen University.The patients\/participants provided their written informed consent to participate in this study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"245"}}