{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:06:08Z","timestamp":1777853168679,"version":"3.51.4"},"reference-count":78,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100005713","name":"Technische Universit\u00e4t M\u00fcnchen","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005713","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Discov Onc"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>ATF3 was found to play a complex role in various cancers; however, its systematic function in kidney renal clear cell carcinoma (KIRC) and across pan-cancer contexts remained incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A comprehensive evaluation of ATF3 expression, diagnostic efficacy, prognostic relevance, and its association with the tumor immune microenvironment was conducted across multiple cancer types using publicly available databases. In KIRC, ATF3 expression in cell lines was validated through real-time quantitative PCR, Western blot, and immunofluorescence tests. Assessments of immune cell infiltration and functional enrichment studies were also carried out. Ultimately, single-cell RNA sequencing (scRNA-seq) were implemented to clarify the role of ATF3 at the cellular level in KIRC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>ATF3 expression was observed to be downregulated in most cancers and was shown to possess diagnostic and prognostic value. Experimentally, ATF3 was confirmed to be downregulated in KIRC cell lines. In KIRC, higher ATF3 expression was connected with an improved outcome. Functional analyses indicated that ATF3 was involved in the IL-17 signaling pathway. The analysis demonstrated that, among seven immune cells with markedly varying infiltration levels, naive B cells and resting memory CD4 T cells were more prevalent in the ATF3 high expression cohort. ScRNA-seq analyses identified endothelial-afferent\/efferent arterioles\/descending vasa recta (AEAs\/DVR) as the key cell, with ATF3 expression primarily detected during the early stage of AEAs\/DVR differentiation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>ATF3 was found downregulated in many cancers and proposed as a pan-cancer biomarker; in KIRC, its low level predicted poor outcome, indicating a potential immunotherapy target.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s12672-026-05113-x","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T22:27:06Z","timestamp":1777501626000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comprehensive analysis of ATF3 as a diagnostic and prognostic biomarker from pan-cancer to clear cell renal cell carcinoma"],"prefix":"10.1007","volume":"17","author":[{"given":"Hao","family":"Ling","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangmei","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanzhu","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"issue":"5","key":"5113_CR1","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1016\/j.eururo.2022.06.016","volume":"82","author":"H Moch","year":"2022","unstructured":"Moch H, Amin MB, Berney DM, Comp\u00e9rat EM, Gill AJ, Hartmann A, et al. The 2022 World Health Organization Classification of Tumours of the Urinary System and Male Genital Organs-Part A: renal, Penile, and Testicular Tumours. Eur Urol. 2022;82(5):458\u201368. https:\/\/doi.org\/10.1016\/j.eururo.2022.06.016.","journal-title":"Eur Urol"},{"issue":"3","key":"5113_CR2","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229\u201363. https:\/\/doi.org\/10.3322\/caac.21834.","journal-title":"CA Cancer J Clin"},{"key":"5113_CR3","doi-asserted-by":"publisher","DOI":"10.3390\/cells13010034","author":"L Meng","year":"2023","unstructured":"Meng L, Collier KA, Wang P, Li Z, Monk P, Mortazavi A, et al. Emerging Immunotherapy Approaches for Advanced Clear Cell Renal Cell Carcinoma. Cells. 2023. https:\/\/doi.org\/10.3390\/cells13010034.","journal-title":"Cells"},{"issue":"3","key":"5113_CR4","doi-asserted-by":"publisher","first-page":"2276629","DOI":"10.1080\/21645515.2023.2276629","volume":"19","author":"A Jang","year":"2023","unstructured":"Jang A, Lichterman JN, Zhong JY, Shoag JE, Garcia JA, Zhang T, et al. Immune approaches beyond traditional immune checkpoint inhibitors for advanced renal cell carcinoma. Hum Vaccin Immunother. 2023;19(3):2276629. https:\/\/doi.org\/10.1080\/21645515.2023.2276629.","journal-title":"Hum Vaccin Immunother"},{"issue":"3 Suppl 7","key":"5113_CR5","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1053\/sonc.2002.33083","volume":"29","author":"JA Glaspy","year":"2002","unstructured":"Glaspy JA. Therapeutic options in the management of renal cell carcinoma. Semin Oncol. 2002;29(3 Suppl 7):41\u20136.","journal-title":"Semin Oncol"},{"issue":"4","key":"5113_CR6","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1038\/ki.2013.245","volume":"84","author":"OCY Yang","year":"2013","unstructured":"Yang OCY, Maxwell PH, Pollard PJ. Renal cell carcinoma: translational aspects of metabolism and therapeutic consequences. Kidney Int. 2013;84(4):667\u201381. https:\/\/doi.org\/10.1038\/ki.2013.245.","journal-title":"Kidney Int"},{"issue":"1","key":"5113_CR7","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s12935-025-04133-x","volume":"26","author":"H Dai","year":"2026","unstructured":"Dai H, Zhang X, Yin L, Chen H, Liu K, Li J, et al. Integrating machine learning and multi-omics analysis to explore Treg-associated programmed cell death features in clear cell renal cell carcinoma. Cancer Cell Int. 2026;26(1):15. https:\/\/doi.org\/10.1186\/s12935-025-04133-x.","journal-title":"Cancer Cell Int"},{"issue":"1","key":"5113_CR8","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/s13008-025-00172-y","volume":"20","author":"H Dai","year":"2025","unstructured":"Dai H, Wang X, Wu Q, Tan Y, Shen H, Gu Y, et al. Integrating genetic crosstalk between atherosclerosis and lung adenocarcinoma to advance precision diagnosis and treatment. Cell Div. 2025;20(1):27. https:\/\/doi.org\/10.1186\/s13008-025-00172-y.","journal-title":"Cell Div"},{"issue":"3","key":"5113_CR9","doi-asserted-by":"publisher","first-page":"1695","DOI":"10.1074\/jbc.271.3.1695","volume":"271","author":"G Liang","year":"1996","unstructured":"Liang G, Wolfgang CD, Chen BP, Chen TH, Hai T. ATF3 gene. Genomic organization, promoter, and regulation. J Biol Chem. 1996;271(3):1695\u2013701.","journal-title":"J Biol Chem"},{"issue":"1","key":"5113_CR10","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1093\/nar\/gkp865","volume":"38","author":"K-H Kim","year":"2009","unstructured":"Kim K-H, Jeong J-Y, Surh Y-J, Kim K-W. Expression of stress-response ATF3 is mediated by Nrf2 in astrocytes. Nucleic Acids Res. 2009;38(1):48\u201359. https:\/\/doi.org\/10.1093\/nar\/gkp865.","journal-title":"Nucleic Acids Res"},{"issue":"4","key":"5113_CR11","doi-asserted-by":"publisher","first-page":"362","DOI":"10.3109\/15376516.2011.557876","volume":"21","author":"C-F Cheng","year":"2011","unstructured":"Cheng C-F, Lin H. Acute kidney injury and the potential for ATF3-regulated epigenetic therapy. Toxicol Mech Methods. 2011;21(4):362\u20136. https:\/\/doi.org\/10.3109\/15376516.2011.557876.","journal-title":"Toxicol Mech Methods"},{"issue":"4","key":"5113_CR12","doi-asserted-by":"publisher","first-page":"e2522","DOI":"10.1002\/brb3.2522","volume":"12","author":"N Ma","year":"2022","unstructured":"Ma N, Li G, Fu X. Protective role of activating transcription factor 3 against neuronal damage in rats with cerebral ischemia. Brain Behav. 2022;12(4):e2522. https:\/\/doi.org\/10.1002\/brb3.2522.","journal-title":"Brain Behav"},{"issue":"8","key":"5113_CR13","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1038\/s41440-018-0058-9","volume":"41","author":"C-L Chou","year":"2018","unstructured":"Chou C-L, Li C-H, Lin H, Liao M-H, Wu C-C, Chen J-S, et al. Role of activating transcription factor 3 in fructose-induced metabolic syndrome in mice. Hypertens Res. 2018;41(8):589\u201397. https:\/\/doi.org\/10.1038\/s41440-018-0058-9.","journal-title":"Hypertens Res"},{"issue":"8","key":"5113_CR14","doi-asserted-by":"publisher","first-page":"e46919","DOI":"10.1016\/j.urolonc.2025.02.016","volume":"43","author":"G Lucarelli","year":"2025","unstructured":"Lucarelli G, Lasorsa F, Milella M, d\u2019Amati A, Ingravallo G, Silecchia M, et al. Transcriptomic and proteo-metabolic determinants of the grading system in clear cell renal cell carcinoma. Urol Oncol. 2025;43(8):e46919\u201332. https:\/\/doi.org\/10.1016\/j.urolonc.2025.02.016.","journal-title":"Urol Oncol"},{"issue":"4","key":"5113_CR15","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1080\/14737159.2023.2195553","volume":"23","author":"NA di Meo","year":"2023","unstructured":"di Meo NA, Lasorsa F, Rutigliano M, Milella M, Ferro M, Battaglia M, et al. The dark side of lipid metabolism in prostate and renal carcinoma: novel insights into molecular diagnostic and biomarker discovery. Expert Rev Mol Diagn. 2023;23(4):297\u2013313. https:\/\/doi.org\/10.1080\/14737159.2023.2195553.","journal-title":"Expert Rev Mol Diagn"},{"issue":"5","key":"5113_CR16","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1080\/14737159.2019.1607729","volume":"19","author":"G Lucarelli","year":"2019","unstructured":"Lucarelli G, Loizzo D, Franzin R, Battaglia S, Ferro M, Cantiello F, et al. Metabolomic insights into pathophysiological mechanisms and biomarker discovery in clear cell renal cell carcinoma. Expert Rev Mol Diagn. 2019;19(5):397\u2013407. https:\/\/doi.org\/10.1080\/14737159.2019.1607729.","journal-title":"Expert Rev Mol Diagn"},{"key":"5113_CR17","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232214360","author":"NA di Meo","year":"2022","unstructured":"di Meo NA, Lasorsa F, Rutigliano M, Loizzo D, Ferro M, Stella A, et al. Renal Cell Carcinoma as a Metabolic Disease: an Update on Main Pathways, Potential Biomarkers, and Therapeutic Targets. Int J Mol Sci. 2022. https:\/\/doi.org\/10.3390\/ijms232214360.","journal-title":"Int J Mol Sci"},{"issue":"8","key":"5113_CR18","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1002\/1873-3468.14531","volume":"597","author":"S De Marco","year":"2023","unstructured":"De Marco S, Torsello B, Minutiello E, Morabito I, Grasselli C, Bombelli S, et al. The cross-talk between Abl2 tyrosine kinase and TGFbeta1 signalling modulates the invasion of clear cell Renal Cell Carcinoma cells. FEBS Lett. 2023;597(8):1098\u2013113. https:\/\/doi.org\/10.1002\/1873-3468.14531.","journal-title":"FEBS Lett"},{"issue":"12","key":"5113_CR19","doi-asserted-by":"publisher","first-page":"3957","DOI":"10.18632\/aging.101685","volume":"10","author":"G Lucarelli","year":"2018","unstructured":"Lucarelli G, Rutigliano M, Sallustio F, Ribatti D, Giglio A, Lepore Signorile M, et al. Integrated multi-omics characterization reveals a distinctive metabolic signature and the role of NDUFA4L2 in promoting angiogenesis, chemoresistance, and mitochondrial dysfunction in clear cell renal cell carcinoma. Aging. 2018;10(12):3957\u201385. https:\/\/doi.org\/10.18632\/aging.101685.","journal-title":"Aging"},{"issue":"69","key":"5113_CR20","doi-asserted-by":"publisher","first-page":"113502","DOI":"10.18632\/oncotarget.23056","volume":"8","author":"C Bianchi","year":"2017","unstructured":"Bianchi C, Meregalli C, Bombelli S, Di Stefano V, Salerno F, Torsello B, et al. The glucose and lipid metabolism reprogramming is grade-dependent in clear cell renal cell carcinoma primary cultures and is targetable to modulate cell viability and proliferation. Oncotarget. 2017;8(69):113502\u201315. https:\/\/doi.org\/10.18632\/oncotarget.23056.","journal-title":"Oncotarget"},{"key":"5113_CR21","doi-asserted-by":"publisher","unstructured":"Ragone R, Sallustio F, Piccinonna S, Rutigliano M, Vanessa G, Palazzo S et al. Renal Cell Carcinoma: a Study through NMR-Based Metabolomics Combined with Transcriptomics, Diseases. 2016. https:\/\/doi.org\/10.3390\/diseases4010007.","DOI":"10.3390\/diseases4010007"},{"issue":"15","key":"5113_CR22","doi-asserted-by":"publisher","first-page":"13371","DOI":"10.18632\/oncotarget.3823","volume":"6","author":"G Lucarelli","year":"2015","unstructured":"Lucarelli G, Galleggiante V, Rutigliano M, Sanguedolce F, Cagiano S, Bufo P, et al. Metabolomic profile of glycolysis and the pentose phosphate pathway identifies the central role of glucose-6-phosphate dehydrogenase in clear cell-renal cell carcinoma. Oncotarget. 2015;6(15):13371\u201386. https:\/\/doi.org\/10.18632\/oncotarget.3823.","journal-title":"Oncotarget"},{"key":"5113_CR23","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232213968","author":"G Lucarelli","year":"2022","unstructured":"Lucarelli G, Rutigliano M, Loizzo D, di Meo NA, Lasorsa F, Mastropasqua M, et al. MUC1 Tissue Expression and Its Soluble Form CA15-3 Identify a Clear Cell Renal Cell Carcinoma with Distinct Metabolic Profile and Poor Clinical Outcome. Int J Mol Sci. 2022. https:\/\/doi.org\/10.3390\/ijms232213968.","journal-title":"Int J Mol Sci"},{"issue":"1","key":"5113_CR24","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1007\/s10238-026-02042-5","volume":"26","author":"G Lucarelli","year":"2026","unstructured":"Lucarelli G, Lasorsa F, Milella M, d\u2019Amati A, Ingravallo G, Di Bari A, et al. MUC1\/CA15-3 identifies a clear cell renal carcinoma characterized by Sunitinib response with a specific metabolic signature. Clin Exp Med. 2026;26(1):106. https:\/\/doi.org\/10.1007\/s10238-026-02042-5.","journal-title":"Clin Exp Med"},{"key":"5113_CR25","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241713179","author":"F Lasorsa","year":"2023","unstructured":"Lasorsa F, Rutigliano M, Milella M, Ferro M, Pandolfo SD, Crocetto F, et al. Cancer Stem Cells in Renal Cell Carcinoma: origins and Biomarkers. Int J Mol Sci. 2023. https:\/\/doi.org\/10.3390\/ijms241713179.","journal-title":"Int J Mol Sci"},{"key":"5113_CR26","doi-asserted-by":"publisher","unstructured":"Milella M, Rutigliano M, Pandolfo SD, Aveta A, Crocetto F, Ferro M et al. The Metabolic Landscape of Cancer Stem Cells: insights and Implications for Therapy. Cells. 2025. https:\/\/doi.org\/10.3390\/cells14100717","DOI":"10.3390\/cells14100717"},{"issue":"3","key":"5113_CR27","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1016\/j.jdermsci.2017.06.005","volume":"87","author":"S M\u00fcller","year":"2017","unstructured":"M\u00fcller S, Smatlik N, Burian M, Ghoreschi K, R\u00f6cken M, Yazdi AS. Differential induction of ATF3 and HO-1 in myeloid cells and keratinocytes via Dimethylfumarate or Cyclosporine A. J Dermatol Sci. 2017;87(3):246\u201351. https:\/\/doi.org\/10.1016\/j.jdermsci.2017.06.005.","journal-title":"J Dermatol Sci"},{"key":"5113_CR28","doi-asserted-by":"publisher","first-page":"107666","DOI":"10.1016\/j.phrs.2025.107666","volume":"214","author":"X Zhao","year":"2025","unstructured":"Zhao X, Chen C, Qiu H, Liu J, Shao N, Guo M, et al. The landscape of ATF3 in tumors: metabolism, expression regulation, therapy approach, and open concerns. Pharmacol Res. 2025;214:107666. https:\/\/doi.org\/10.1016\/j.phrs.2025.107666.","journal-title":"Pharmacol Res"},{"key":"5113_CR29","doi-asserted-by":"publisher","first-page":"618987","DOI":"10.3389\/fcell.2021.618987","volume":"9","author":"S Gao","year":"2021","unstructured":"Gao S, Gao L, Wang S, Shi X, Yue C, Wei S, et al. ATF3 Suppresses Growth and Metastasis of Clear Cell Renal Cell Carcinoma by Deactivating EGFR\/AKT\/GSK3beta\/beta-Catenin Signaling Pathway. Front Cell Dev Biol. 2021;9:618987. https:\/\/doi.org\/10.3389\/fcell.2021.618987.","journal-title":"Front Cell Dev Biol"},{"issue":"1","key":"5113_CR30","doi-asserted-by":"publisher","first-page":"5029","DOI":"10.1038\/s41467-023-40271-4","volume":"14","author":"R Arora","year":"2023","unstructured":"Arora R, Cao C, Kumar M, Sinha S, Chanda A, McNeil R, et al. Spatial transcriptomics reveals distinct and conserved tumor core and edge architectures that predict survival and targeted therapy response. Nat Commun. 2023;14(1):5029. https:\/\/doi.org\/10.1038\/s41467-023-40271-4.","journal-title":"Nat Commun"},{"key":"5113_CR31","doi-asserted-by":"publisher","first-page":"1008605","DOI":"10.3389\/fsurg.2023.1008605","volume":"10","author":"YA Jiang","year":"2023","unstructured":"Jiang YA, Chen P, Liang J, Long X, Cai J, Zhang Y, et al. Clinical diagnosis model of spinal meningiomas based on the surveillance, epidemiology, and end results database. Front Surg. 2023;10:1008605. https:\/\/doi.org\/10.3389\/fsurg.2023.1008605.","journal-title":"Front Surg"},{"issue":"4","key":"5113_CR32","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1200\/JCO.18.00283","volume":"37","author":"A Latham","year":"2018","unstructured":"Latham A, Srinivasan P, Kemel Y, Shia J, Bandlamudi C, Mandelker D, et al. Microsatellite Instability Is Associated With the Presence of Lynch Syndrome Pan-Cancer. J Clin Oncol. 2018;37(4):286\u201395. https:\/\/doi.org\/10.1200\/JCO.18.00283.","journal-title":"J Clin Oncol"},{"issue":"2","key":"5113_CR33","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1038\/nrg.2017.80","volume":"19","author":"F Lyko","year":"2017","unstructured":"Lyko F. The DNA methyltransferase family: a versatile toolkit for epigenetic regulation. Nat Rev Genet. 2017;19(2):81\u201392. https:\/\/doi.org\/10.1038\/nrg.2017.80.","journal-title":"Nat Rev Genet"},{"key":"5113_CR34","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.03.034","author":"TM Malta","year":"2018","unstructured":"Malta TM, Sokolov A, Gentles AJ, Burzykowski T, Poisson L, Weinstein JN, et al. Machine Learning Identifies Stemness Features Associated with Oncogenic Dedifferentiation. Cell. 2018. https:\/\/doi.org\/10.1016\/j.cell.2018.03.034.","journal-title":"Cell"},{"issue":"3","key":"5113_CR35","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1093\/sysbio\/syq010","volume":"59","author":"S Guindon","year":"2010","unstructured":"Guindon S, Dufayard J-F, Lefort V, Anisimova M, Hordijk W, Gascuel O. New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0. Syst Biol. 2010;59(3):307\u201321. https:\/\/doi.org\/10.1093\/sysbio\/syq010.","journal-title":"Syst Biol"},{"issue":"12","key":"5113_CR36","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15(12):550.","journal-title":"Genome Biol"},{"issue":"1","key":"5113_CR37","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1186\/s12864-023-09677-8","volume":"24","author":"T Cao","year":"2023","unstructured":"Cao T, Li Q, Huang Y, Li A. plotnineSeqSuite: a Python package for visualizing sequence data using ggplot2 style. BMC Genomics. 2023;24(1):585. https:\/\/doi.org\/10.1186\/s12864-023-09677-8.","journal-title":"BMC Genomics"},{"issue":"5","key":"5113_CR38","doi-asserted-by":"publisher","first-page":"1460","DOI":"10.1093\/bioinformatics\/btab806","volume":"38","author":"Z Gu","year":"2022","unstructured":"Gu Z, H\u00fcbschmann D. Make Interactive Complex Heatmaps in R. Bioinformatics. 2022;38(5):1460\u20132. https:\/\/doi.org\/10.1093\/bioinformatics\/btab806.","journal-title":"Bioinformatics"},{"issue":"5","key":"5113_CR39","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","volume":"16","author":"G Yu","year":"2012","unstructured":"Yu G, Wang L-G, Han Y, He Q-Y. clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS. 2012;16(5):284\u20137. https:\/\/doi.org\/10.1089\/omi.2011.0118.","journal-title":"OMICS"},{"issue":"1","key":"5113_CR40","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/s12969-023-00949-x","volume":"22","author":"P Ding","year":"2024","unstructured":"Ding P, Du Y, Jiang X, Chen H, Huang L. Establishment and analysis of a novel diagnostic model for systemic juvenile idiopathic arthritis based on machine learning. Pediatr Rheumatol Online J. 2024;22(1):18. https:\/\/doi.org\/10.1186\/s12969-023-00949-x.","journal-title":"Pediatr Rheumatol Online J"},{"key":"5113_CR41","doi-asserted-by":"publisher","unstructured":"Maeser D, Gruener RF, Huang RS. oncoPredict: an R package for predicting in vivo or cancer patient drug response and biomarkers from cell line screening data. Brief Bioinform. 2021. https:\/\/doi.org\/10.1093\/bib\/bbab260.","DOI":"10.1093\/bib\/bbab260"},{"issue":"2","key":"5113_CR42","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1038\/s41587-023-01767-y","volume":"42","author":"Y Hao","year":"2023","unstructured":"Hao Y, Stuart T, Kowalski MH, Choudhary S, Hoffman P, Hartman A, et al. Dictionary learning for integrative, multimodal and scalable single-cell analysis. Nat Biotechnol. 2023;42(2):293\u2013304. https:\/\/doi.org\/10.1038\/s41587-023-01767-y.","journal-title":"Nat Biotechnol"},{"key":"5113_CR43","doi-asserted-by":"publisher","unstructured":"Zhang Y, Narayanan SP, Mannan R, Raskind G, Wang X, Vats P, et al. Single-cell analyses of renal cell cancers reveal insights into tumor microenvironment, cell of origin, and therapy response. Proc Natl Acad Sci USA. 2021;118(24). https:\/\/doi.org\/10.1073\/pnas.2103240118.","DOI":"10.1073\/pnas.2103240118"},{"key":"5113_CR44","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2019.03.003","author":"CS McGinnis","year":"2019","unstructured":"McGinnis CS, Murrow LM, Gartner ZJ. DoubletFinder: doublet Detection in Single-Cell RNA Sequencing Data Using Artificial Nearest Neighbors. Cell Syst. 2019. https:\/\/doi.org\/10.1016\/j.cels.2019.03.003.","journal-title":"Cell Syst"},{"key":"5113_CR45","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.jtos.2024.06.005","volume":"34","author":"D Huang","year":"2024","unstructured":"Huang D, Jiao X, Huang S, Liu J, Si H, Qi D, et al. Analysis of the heterogeneity and complexity of murine extraorbital lacrimal gland via single-cell RNA sequencing. Ocul Surf. 2024;34:60\u201395. https:\/\/doi.org\/10.1016\/j.jtos.2024.06.005.","journal-title":"Ocul Surf"},{"issue":"3","key":"5113_CR46","doi-asserted-by":"publisher","first-page":"121","DOI":"10.31083\/j.fbl2903121","volume":"29","author":"B Chen","year":"2024","unstructured":"Chen B, Zhou M, Guo L, Huang H, Sun X, Peng Z, et al. An Integrated Machine Learning Framework Identifies Prognostic Gene Pair Biomarkers Associated with Programmed Cell Death Modalities in Clear Cell Renal Cell Carcinoma. Front Biosci (Landmark Ed). 2024;29(3):121. https:\/\/doi.org\/10.31083\/j.fbl2903121.","journal-title":"Front Biosci (Landmark Ed)"},{"key":"5113_CR47","doi-asserted-by":"publisher","first-page":"394632024122732","DOI":"10.1177\/03946320241227320","volume":"38","author":"Z Yang","year":"2024","unstructured":"Yang Z, Hou Y, Li J, Xu D, Yang Z, Wang X. Activating transcription factor 3 is a new biomarker correlation with renal clear cell carcinoma progression. Int J Immunopathol Pharmacol. 2024;38:3946320241227320. https:\/\/doi.org\/10.1177\/03946320241227320.","journal-title":"Int J Immunopathol Pharmacol"},{"issue":"10","key":"5113_CR48","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1158\/2159-8290.CD-19-0499","volume":"9","author":"L Vuong","year":"2019","unstructured":"Vuong L, Kotecha RR, Voss MH, Hakimi AA. Tumor Microenvironment Dynamics in Clear-Cell Renal Cell Carcinoma. Cancer Discov. 2019;9(10):1349\u201357. https:\/\/doi.org\/10.1158\/2159-8290.CD-19-0499.","journal-title":"Cancer Discov"},{"issue":"6","key":"5113_CR49","doi-asserted-by":"publisher","first-page":"e35511","DOI":"10.1016\/j.urolonc.2019.01.025","volume":"37","author":"R Tamma","year":"2019","unstructured":"Tamma R, Rutigliano M, Lucarelli G, Annese T, Ruggieri S, Cascardi E, et al. Microvascular density, macrophages, and mast cells in human clear cell renal carcinoma with and without bevacizumab treatment. Urol Oncol. 2019;37(6):e35511\u20139. https:\/\/doi.org\/10.1016\/j.urolonc.2019.01.025.","journal-title":"Urol Oncol"},{"key":"5113_CR50","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1186\/s12967-016-0841-9","volume":"14","author":"M Gigante","year":"2016","unstructured":"Gigante M, Pontrelli P, Herr W, Gigante M, D\u2019Avenia M, Zaza G, et al. miR-29b and miR-198 overexpression in CD8\u2009+\u2009T cells of renal cell carcinoma patients down-modulates JAK3 and MCL-1 leading to immune dysfunction. J translational Med. 2016;14:84. https:\/\/doi.org\/10.1186\/s12967-016-0841-9.","journal-title":"J translational Med"},{"key":"5113_CR51","doi-asserted-by":"publisher","DOI":"10.3390\/ijms242216515","author":"F Lasorsa","year":"2023","unstructured":"Lasorsa F, Rutigliano M, Milella M, Ferro M, Pandolfo SD, Crocetto F, et al. Complement System and the Kidney: its Role in Renal Diseases, Kidney Transplantation and Renal Cell Carcinoma. Int J Mol Sci. 2023. https:\/\/doi.org\/10.3390\/ijms242216515.","journal-title":"Int J Mol Sci"},{"key":"5113_CR52","doi-asserted-by":"publisher","unstructured":"Lasorsa F, di Meo NA, Rutigliano M, Milella M, Ferro M, Pandolfo SD, et al. Immune Checkpoint Inhibitors in Renal Cell Carcinoma: molecular Basis and Rationale for Their Use in Clinical Practice. Biomedicines. 2023. https:\/\/doi.org\/10.3390\/biomedicines11041071","DOI":"10.3390\/biomedicines11041071"},{"key":"5113_CR53","doi-asserted-by":"publisher","unstructured":"Ghini V, Laera L, Fantechi B, Monte FD, Benelli M, McCartney A, et al. Metabolomics to Assess Response to Immune Checkpoint Inhibitors in Patients with Non-Small-Cell Lung Cancer. Cancers (Basel). 2020. https:\/\/doi.org\/10.3390\/cancers12123574.","DOI":"10.3390\/cancers12123574"},{"key":"5113_CR54","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24054814","author":"G Lucarelli","year":"2023","unstructured":"Lucarelli G, Netti GS, Rutigliano M, Lasorsa F, Loizzo D, Milella M, et al. MUC1 Expression Affects the Immunoflogosis in Renal Cell Carcinoma Microenvironment through Complement System Activation and Immune Infiltrate Modulation. Int J Mol Sci. 2023. https:\/\/doi.org\/10.3390\/ijms24054814.","journal-title":"Int J Mol Sci"},{"key":"5113_CR55","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12123888","author":"F Lasorsa","year":"2023","unstructured":"Lasorsa F, Rutigliano M, Milella M, Ferro M, Pandolfo SD, Crocetto F, et al. Cellular and Molecular Players in the Tumor Microenvironment of Renal Cell Carcinoma. J Clin Med. 2023. https:\/\/doi.org\/10.3390\/jcm12123888.","journal-title":"J Clin Med"},{"issue":"9","key":"5113_CR56","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1080\/17568919.2025.2498876","volume":"17","author":"F Lasorsa","year":"2025","unstructured":"Lasorsa F, Rutigliano M, Milella M, Ditonno P, Lucarelli G. Targeting the complement system: notes on therapeutic strategies for renal cancer. Future Med Chem. 2025;17(9):979\u201381. https:\/\/doi.org\/10.1080\/17568919.2025.2498876.","journal-title":"Future Med Chem"},{"issue":"8","key":"5113_CR57","doi-asserted-by":"publisher","first-page":"7585","DOI":"10.18632\/aging.103169","volume":"12","author":"GS Netti","year":"2020","unstructured":"Netti GS, Lucarelli G, Spadaccino F, Castellano G, Gigante M, Divella C, et al. PTX3 modulates the immunoflogosis in tumor microenvironment and is a prognostic factor for patients with clear cell renal cell carcinoma. Aging. 2020;12(8):7585\u2013602. https:\/\/doi.org\/10.18632\/aging.103169.","journal-title":"Aging"},{"issue":"7","key":"5113_CR58","doi-asserted-by":"publisher","first-page":"e46115","DOI":"10.1016\/j.urolonc.2017.02.011","volume":"35","author":"G Lucarelli","year":"2017","unstructured":"Lucarelli G, Rutigliano M, Ferro M, Giglio A, Intini A, Triggiano F, et al. Activation of the kynurenine pathway predicts poor outcome in patients with clear cell renal cell carcinoma. Urol Oncol. 2017;35(7):e46115\u201327. https:\/\/doi.org\/10.1016\/j.urolonc.2017.02.011.","journal-title":"Urol Oncol"},{"key":"5113_CR59","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3003284","author":"Y Qiu","year":"2025","unstructured":"Qiu Y, Xu Y, Ding X, Zhao C, Cheng H, Li G. Bi-directional metabolic reprogramming between cancer cells and T cells reshapes the anti-tumor immune response. PLoS Biol. 2025. https:\/\/doi.org\/10.1371\/journal.pbio.3003284.","journal-title":"PLoS Biol"},{"key":"5113_CR60","doi-asserted-by":"publisher","DOI":"10.3390\/ijms242417422","author":"X Zhang","year":"2023","unstructured":"Zhang X, Song W, Gao Y, Zhang Y, Zhao Y, Hao S, et al. The Role of Tumor Metabolic Reprogramming in Tumor Immunity. Int J Mol Sci. 2023. https:\/\/doi.org\/10.3390\/ijms242417422.","journal-title":"Int J Mol Sci"},{"key":"5113_CR61","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1038\/s41590-020-0725-2","volume":"21","author":"S Vardhana","year":"2020","unstructured":"Vardhana S, Hwee M, Berisa M, Wells D, Yost K, King B, et al. Impaired mitochondrial oxidative phosphorylation limits the self-renewal of T cells exposed to persistent antigen. Nat Immunol. 2020;21:1022\u201333. https:\/\/doi.org\/10.1038\/s41590-020-0725-2.","journal-title":"Nat Immunol"},{"key":"5113_CR62","doi-asserted-by":"publisher","DOI":"10.1007\/s13402-023-00801-0","author":"X Qiu","year":"2023","unstructured":"Qiu X, Li Y, Zhang Z. Crosstalk between oxidative phosphorylation and immune escape in cancer: a new concept of therapeutic targets selection. Cell Oncol. 2023. https:\/\/doi.org\/10.1007\/s13402-023-00801-0.","journal-title":"Cell Oncol"},{"issue":"8038","key":"5113_CR63","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1038\/s41586-024-08049-w","volume":"635","author":"Y Hou","year":"2024","unstructured":"Hou Y, Sun L, LaFleur MW, Huang L, Lambden C, Thakore PI, et al. Neuropeptide signalling orchestrates T cell differentiation. Nature. 2024;635(8038):444\u201352. https:\/\/doi.org\/10.1038\/s41586-024-08049-w.","journal-title":"Nature"},{"issue":"12","key":"5113_CR64","doi-asserted-by":"publisher","first-page":"1186","DOI":"10.1002\/dneu.20934","volume":"71","author":"DL Moore","year":"2011","unstructured":"Moore DL, Goldberg JL. Multiple transcription factor families regulate axon growth and regeneration. Dev Neurobiol. 2011;71(12):1186\u2013211. https:\/\/doi.org\/10.1002\/dneu.20934.","journal-title":"Dev Neurobiol"},{"issue":"5","key":"5113_CR65","doi-asserted-by":"publisher","first-page":"1164","DOI":"10.1016\/j.cmet.2024.04.002","volume":"36","author":"Z Lu","year":"2024","unstructured":"Lu Z, McBrearty N, Chen J, Tomar VS, Zhang H, De Rosa G, et al. ATF3 and CH25H regulate effector trogocytosis and anti-tumor activities of endogenous and immunotherapeutic cytotoxic T lymphocytes. Cell Metab. 2024;36(5):1164\u20137. https:\/\/doi.org\/10.1016\/j.cmet.2024.04.002.","journal-title":"Cell Metab"},{"issue":"10","key":"5113_CR66","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1016\/j.urolonc.2019.04.028","volume":"38","author":"RG DiNatale","year":"2020","unstructured":"DiNatale RG, Sanchez A, Hakimi AA, Reznik E. Metabolomics informs common patterns of molecular dysfunction across histologies of renal cell carcinoma. Urol Oncol. 2020;38(10):755\u201362. https:\/\/doi.org\/10.1016\/j.urolonc.2019.04.028.","journal-title":"Urol Oncol"},{"key":"5113_CR67","doi-asserted-by":"publisher","first-page":"101476","DOI":"10.1016\/j.smim.2021.101476","volume":"52","author":"A Glasner","year":"2021","unstructured":"Glasner A, Plitas G. Tumor resident regulatory T cells. Semin Immunol. 2021;52:101476. https:\/\/doi.org\/10.1016\/j.smim.2021.101476.","journal-title":"Semin Immunol"},{"key":"5113_CR68","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1007\/978-3-030-49270-0_6","volume":"1273","author":"RE Dadey","year":"2020","unstructured":"Dadey RE, Workman CJ, Vignali DAA. Regulatory T Cells in the Tumor Microenvironment. Adv Exp Med Biol. 2020;1273:105\u201334. https:\/\/doi.org\/10.1007\/978-3-030-49270-0_6.","journal-title":"Adv Exp Med Biol"},{"issue":"12","key":"5113_CR69","doi-asserted-by":"publisher","first-page":"5483","DOI":"10.4049\/jimmunol.155.12.5483","volume":"155","author":"Z Yao","year":"1995","unstructured":"Yao Z, Painter SL, Fanslow WC, Ulrich D, Macduff BM, Spriggs MK, et al. Human IL-17: a novel cytokine derived from T cells. J Immunol (Baltimore Md : 1950). 1995;155(12):5483\u20136.","journal-title":"J Immunol (Baltimore Md : 1950)"},{"issue":"3","key":"5113_CR70","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1681\/ASN.2014111136","volume":"27","author":"R Mohamed","year":"2016","unstructured":"Mohamed R, Jayakumar C, Chen F, Fulton D, Stepp D, Gansevoort RT, et al. Low-Dose IL-17 Therapy Prevents and Reverses Diabetic Nephropathy, Metabolic Syndrome, and Associated Organ Fibrosis. J Am Soc Nephrol. 2016;27(3):745\u201365. https:\/\/doi.org\/10.1681\/ASN.2014111136.","journal-title":"J Am Soc Nephrol"},{"key":"5113_CR71","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-023-00704-1","author":"E West","year":"2023","unstructured":"West E, Kemper C. Complosome\u2014the intracellular complement system. Nat Rev Nephrol. 2023. https:\/\/doi.org\/10.1038\/s41581-023-00704-1.","journal-title":"Nat Rev Nephrol"},{"key":"5113_CR72","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00001","author":"M Kolev","year":"2017","unstructured":"Kolev M, Kemper C. Keeping It All Going\u2014Complement Meets Metabolism. Front Immunol. 2017. https:\/\/doi.org\/10.3389\/fimmu.2017.00001.","journal-title":"Front Immunol"},{"key":"5113_CR73","doi-asserted-by":"publisher","first-page":"556","DOI":"10.3389\/fendo.2020.00556","volume":"11","author":"H-C Ku","year":"2020","unstructured":"Ku H-C, Cheng C-F. Master Regulator Activating Transcription Factor 3 (ATF3) in Metabolic Homeostasis and Cancer. Front Endocrinol (Lausanne). 2020;11:556. https:\/\/doi.org\/10.3389\/fendo.2020.00556.","journal-title":"Front Endocrinol (Lausanne)"},{"key":"5113_CR74","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-025-07903-7","author":"K Tokumura","year":"2025","unstructured":"Tokumura K, Fukasawa K, Ichikawa J, Sadamori K, Hiraiwa M, Hinoi E. PDK1-dependent metabolic reprogramming regulates stemness and tumorigenicity of osteosarcoma stem cells through ATF3. Cell Death Dis. 2025. https:\/\/doi.org\/10.1038\/s41419-025-07903-7.","journal-title":"Cell Death Dis"},{"issue":"2","key":"5113_CR75","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1152\/physrev.00042.2012","volume":"95","author":"M Carlstr\u00f6m","year":"2015","unstructured":"Carlstr\u00f6m M, Wilcox CS, Arendshorst WJ. Renal autoregulation in health and disease. Physiol Rev. 2015;95(2):405\u2013511. https:\/\/doi.org\/10.1152\/physrev.00042.2012.","journal-title":"Physiol Rev"},{"issue":"8","key":"5113_CR76","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1007\/s00424-022-02690-y","volume":"474","author":"A Edwards","year":"2022","unstructured":"Edwards A, Kurtcuoglu V. Renal blood flow and oxygenation. Pfl\u00fcgers Archiv - Eur J Physiol. 2022;474(8):759\u201370. https:\/\/doi.org\/10.1007\/s00424-022-02690-y.","journal-title":"Pfl\u00fcgers Archiv - Eur J Physiol"},{"issue":"6","key":"5113_CR77","doi-asserted-by":"publisher","first-page":"845","DOI":"10.2174\/15701611113116660149","volume":"12","author":"M Burke","year":"2014","unstructured":"Burke M, Pabbidi MR, Farley J, Roman RJ. Molecular mechanisms of renal blood flow autoregulation. Curr Vasc Pharmacol. 2014;12(6):845\u201358.","journal-title":"Curr Vasc Pharmacol"},{"issue":"6","key":"5113_CR78","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1159\/000261705","volume":"4","author":"C Mundhenke","year":"2009","unstructured":"Mundhenke C, Strauss A, Schem C. Significance of Tyrosine Kinase Inhibitors in the Treatment of Metastatic Breast Cancer. Breast Care (Basel). 2009;4(6):373\u20138. https:\/\/doi.org\/10.1159\/000261705.","journal-title":"Breast Care (Basel)"}],"container-title":["Discover Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12672-026-05113-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12672-026-05113-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12672-026-05113-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T22:49:11Z","timestamp":1777502951000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12672-026-05113-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,30]]},"references-count":78,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["5113"],"URL":"https:\/\/doi.org\/10.1007\/s12672-026-05113-x","relation":{},"ISSN":["2730-6011"],"issn-type":[{"value":"2730-6011","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,30]]},"assertion":[{"value":"20 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 April 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":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"657"}}