{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T10:13:10Z","timestamp":1788775990034,"version":"build-2803163510"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Genes Genom"],"published-print":{"date-parts":[[2026,9]]},"DOI":"10.1007\/s13258-026-01788-2","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T08:11:11Z","timestamp":1783411871000},"page":"1223-1231","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Subtype-specific clinical significance of RRM1 and RRM2 expression in non-small cell lung cancer: a TCGA-based analysis"],"prefix":"10.1007","volume":"48","author":[{"given":"Se-Young","family":"Yun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunha","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junchae","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyowon","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5562-0720","authenticated-orcid":false,"given":"Jae-Ho","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"key":"1788_CR1","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.canlet.2014.01.017","volume":"356","author":"KM Aird","year":"2015","unstructured":"Aird KM, Zhang R (2015) Nucleotide metabolism, oncogene-induced senescence and cancer. Cancer Lett 356:204\u2013210","journal-title":"Cancer Lett"},{"key":"1788_CR2","doi-asserted-by":"publisher","first-page":"1878","DOI":"10.1200\/JCO.2004.12.002","volume":"22","author":"G Bepler","year":"2004","unstructured":"Bepler G, Sharma S, Cantor A et al (2004) RRM1 and PTEN as prognostic parameters for overall and disease-free survival in patients with non-small-cell lung cancer. J Clin Oncol 22:1878\u20131885","journal-title":"J Clin Oncol"},{"key":"1788_CR3","doi-asserted-by":"publisher","first-page":"4731","DOI":"10.1200\/JCO.2006.06.1101","volume":"24","author":"G Bepler","year":"2006","unstructured":"Bepler G, Kusmartseva I, Sharma S et al (2006) RRM1 modulated in vitro and in vivo efficacy of gemcitabine and platinum in non-small-cell lung cancer. J Clin Oncol 24:4731\u20134737","journal-title":"J Clin Oncol"},{"key":"1788_CR4","doi-asserted-by":"publisher","first-page":"1050","DOI":"10.1200\/JCO.2012.43.0900","volume":"31","author":"B Besse","year":"2013","unstructured":"Besse B, Olaussen KA, Soria JC (2013) ERCC1 and RRM1: ready for prime time? J Clin Oncol 31:1050\u20131060","journal-title":"J Clin Oncol"},{"key":"1788_CR5","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1016\/j.cell.2011.03.044","volume":"145","author":"AC Bester","year":"2011","unstructured":"Bester AC, Roniger M, Oren YS et al (2011) Nucleotide deficiency promotes genomic instability in early stages of cancer development. Cell 145:435\u2013446","journal-title":"Cell"},{"key":"1788_CR6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0003695","volume":"3","author":"I Boukovinas","year":"2008","unstructured":"Boukovinas I, Papadaki C, Mendez P et al (2008) Tumor BRCA1, RRM1 and RRM2 mRNA expression levels and clinical response to first-line gemcitabine plus docetaxel in non-small-cell lung cancer patients. PLoS ONE 3:e3695","journal-title":"PLoS ONE"},{"key":"1788_CR7","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1038\/ng.3564","volume":"48","author":"JD Campbell","year":"2016","unstructured":"Campbell JD, Alexandrov A, Kim J et al (2016) Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas. Nat Genet 48:607\u2013616","journal-title":"Nat Genet"},{"key":"1788_CR8","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1038\/nature11404","volume":"489","author":"Cancer Genome Atlas Research Network","year":"2012","unstructured":"Cancer Genome Atlas Research Network (2012) Comprehensive genomic characterization of squamous cell lung cancers. Nature 489:519\u2013525","journal-title":"Nature"},{"key":"1788_CR9","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1038\/nature13385","volume":"511","author":"Cancer Genome Atlas Research Network","year":"2014","unstructured":"Cancer Genome Atlas Research Network (2014) Comprehensive molecular profiling of lung adenocarcinoma. Nature 511:543\u2013550","journal-title":"Nature"},{"key":"1788_CR10","doi-asserted-by":"publisher","first-page":"3213","DOI":"10.1038\/s41467-019-11214-9","volume":"10","author":"G Chen","year":"2019","unstructured":"Chen G, Luo Y, Warncke K et al (2019) Acetylation regulates ribonucleotide reductase activity and cancer cell growth. Nat Commun 10:3213","journal-title":"Nat Commun"},{"key":"1788_CR11","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1016\/j.cell.2012.03.043","volume":"149","author":"V D\u2019Angiolella","year":"2012","unstructured":"D\u2019Angiolella V, Donato V, Forrester FM et al (2012) Cyclin F-mediated degradation of ribonucleotide reductase M2 controls genome integrity and DNA repair. Cell 149:1023\u20131034","journal-title":"Cell"},{"key":"1788_CR12","doi-asserted-by":"publisher","first-page":"3761","DOI":"10.1158\/0008-5472.CAN-03-3363","volume":"64","author":"JD Davidson","year":"2004","unstructured":"Davidson JD, Ma L, Flagella M et al (2004) Increased expression of ribonucleotide reductase large subunit 1 is associated with gemcitabine resistance in non-small cell lung cancer cell lines. Cancer Res 64:3761\u20133766","journal-title":"Cancer Res"},{"key":"1788_CR13","first-page":"4204","volume":"59","author":"YG Goan","year":"1999","unstructured":"Goan YG, Zhou B, Hu E et al (1999) Overexpression of ribonucleotide reductase as a mechanism of resistance to 2,2-difluorodeoxycytidine in the human KB cancer cell line. Cancer Res 59:4204\u20134207","journal-title":"Cancer Res"},{"key":"1788_CR15","doi-asserted-by":"publisher","first-page":"R435","DOI":"10.1016\/j.cub.2014.04.012","volume":"24","author":"SA Hills","year":"2014","unstructured":"Hills SA, Diffley JFX (2014) DNA replication and oncogene-induced replicative stress. Curr Biol 24:R435\u2013R444","journal-title":"Curr Biol"},{"key":"1788_CR16","doi-asserted-by":"publisher","first-page":"3518","DOI":"10.18632\/aging.202292","volume":"13","author":"CY Jin","year":"2020","unstructured":"Jin CY, Du L, Nuerlan AH et al (2020) High expression of RRM2 as an independent predictive factor of poor prognosis in patients with lung adenocarcinoma. Aging (Albany NY) 13:3518\u20133535","journal-title":"Aging (Albany NY)"},{"key":"1788_CR17","doi-asserted-by":"publisher","first-page":"4601","DOI":"10.3390\/cancers13184601","volume":"13","author":"U Jo","year":"2021","unstructured":"Jo U, Murai Y, Takebe N et al (2021) Precision oncology with drugs targeting replication stress, ATR, and Schlafen 11. Cancers (Basel) 13:4601","journal-title":"Cancers (Basel)"},{"key":"1788_CR18","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1038\/nrd4010","volume":"12","author":"LP Jordheim","year":"2013","unstructured":"Jordheim LP, Durantel D, Zoulim F et al (2013) Advances in the development of nucleoside and nucleotide analogues for cancer and viral diseases. Nat Rev Drug Discov 12:447\u2013464","journal-title":"Nat Rev Drug Discov"},{"key":"1788_CR19","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1007\/s13258-024-01604-9","volume":"47","author":"S Keum","year":"2025","unstructured":"Keum S, Lee YJ, Kim JW, Rhee S (2025) Dual-specificity phosphatase 23 functions as a promising prognostic biomarker in non-small cell lung cancer. Genes Genomics 47:321\u2013329","journal-title":"Genes Genomics"},{"key":"1788_CR20","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1007\/s13258-025-01671-6","volume":"47","author":"TY Kim","year":"2025","unstructured":"Kim TY, Bae AN, Lee JH (2025) EIF5B as a prognostic biomarker and its correlation with infiltrating immune cells in liver cancer. Genes Genomics 47:1039\u20131048","journal-title":"Genes Genomics"},{"key":"1788_CR21","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1038\/s41568-018-0034-3","volume":"18","author":"E Lecona","year":"2018","unstructured":"Lecona E, Fernandez-Capetillo O (2018) Targeting ATR in cancer. Nat Rev Cancer 18:586\u2013595","journal-title":"Nat Rev Cancer"},{"key":"1788_CR22","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1097\/FPC.0b013e32834dd7e2","volume":"22","author":"L Li","year":"2012","unstructured":"Li L, Schaid DJ, Fridley BL et al (2012) Gemcitabine metabolic pathway genetic polymorphisms and response in patients with non-small cell lung cancer. Pharmacogenet Genomics 22:105\u2013116","journal-title":"Pharmacogenet Genomics"},{"key":"1788_CR23","doi-asserted-by":"publisher","first-page":"7009","DOI":"10.7150\/jca.47895","volume":"11","author":"C Ma","year":"2020","unstructured":"Ma C, Luo H, Cao J et al (2020) Independent prognostic implications of RRM2 in lung adenocarcinoma. J Cancer 11:7009\u20137022","journal-title":"J Cancer"},{"key":"1788_CR24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0127600","volume":"10","author":"V Mah","year":"2015","unstructured":"Mah V, Alavi M, M\u00e1rquez-Garb\u00e1n DC et al (2015) Ribonucleotide reductase subunit M2 predicts survival in subgroups of patients with non-small cell lung carcinoma. PLoS ONE 10:e0127600","journal-title":"PLoS ONE"},{"key":"1788_CR25","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1038\/nrc3981","volume":"15","author":"CK Mathews","year":"2015","unstructured":"Mathews CK (2015) Deoxyribonucleotide metabolism, mutagenesis and cancer. Nat Rev Cancer 15:528\u2013539","journal-title":"Nat Rev Cancer"},{"key":"1788_CR26","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1097\/JTO.0b013e318287c3c5","volume":"8","author":"MK Maus","year":"2013","unstructured":"Maus MK, Mack PC, Astrow SH et al (2013) Histology-related associations of ERCC1, RRM1, and TS biomarkers in patients with non-small-cell lung cancer. J Thorac Oncol 8:582\u2013586","journal-title":"J Thorac Oncol"},{"key":"1788_CR27","first-page":"329","volume":"38","author":"HJ Moon","year":"2025","unstructured":"Moon HJ, Cha Y, Lee JH et al (2025) Clinical and prognostic value of TIMP1 in colorectal cancer. Anat Biol Anthropol 38:329\u2013334","journal-title":"Anat Biol Anthropol"},{"key":"1788_CR28","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1146\/annurev.biochem.75.103004.142443","volume":"75","author":"P Nordlund","year":"2006","unstructured":"Nordlund P, Reichard P (2006) Ribonucleotide reductases. Annu Rev Biochem 75:681\u2013706","journal-title":"Annu Rev Biochem"},{"key":"1788_CR29","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1016\/j.molcel.2015.10.040","volume":"60","author":"MJ O\u2019Connor","year":"2015","unstructured":"O\u2019Connor MJ (2015) Targeting the DNA damage response in cancer. Mol Cell 60:547\u2013560","journal-title":"Mol Cell"},{"key":"1788_CR30","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1016\/j.jconrel.2012.01.045","volume":"159","author":"MA Rahman","year":"2012","unstructured":"Rahman MA, Amin AR, Wang X et al (2012) Systemic delivery of siRNA nanoparticles targeting RRM2 suppresses tumor growth. J Control Release 159:384\u2013392","journal-title":"J Control Release"},{"key":"1788_CR31","doi-asserted-by":"publisher","first-page":"3416","DOI":"10.1158\/1078-0432.CCR-13-0073","volume":"19","author":"MA Rahman","year":"2013","unstructured":"Rahman MA, Amin AR, Wang D et al (2013) RRM2 regulates Bcl-2 in head and neck and lung cancers. Clin Cancer Res 19:3416\u20133428","journal-title":"Clin Cancer Res"},{"key":"1788_CR32","doi-asserted-by":"publisher","first-page":"3548","DOI":"10.1038\/sj.onc.1206419","volume":"22","author":"R Rosell","year":"2003","unstructured":"Rosell R, Scagliotti G, Danenberg KD et al (2003) Transcripts in pretreatment biopsies. Oncogene 22:3548\u20133553","journal-title":"Oncogene"},{"key":"1788_CR33","doi-asserted-by":"publisher","first-page":"1318","DOI":"10.1158\/1078-0432.CCR-03-0156","volume":"10","author":"R Rosell","year":"2004","unstructured":"Rosell R, Danenberg KD, Alberola V et al (2004) Ribonucleotide reductase mRNA expression and survival. Clin Cancer Res 10:1318\u20131325","journal-title":"Clin Cancer Res"},{"key":"1788_CR34","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1007\/s13258-024-01606-7","volume":"47","author":"S Song","year":"2025","unstructured":"Song S, Rhee S (2025) CKAP4 is a potential therapeutic target to overcome resistance to EGFR-TKIs in lung adenocarcinoma. Genes Genomics 47:331\u2013340","journal-title":"Genes Genomics"},{"key":"1788_CR35","first-page":"209","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel RL et al (2021) Global cancer statistics 2020. CA Cancer J Clin 71:209\u2013249","journal-title":"CA Cancer J Clin"},{"key":"1788_CR36","doi-asserted-by":"publisher","first-page":"1899","DOI":"10.1007\/s13277-013-1255-4","volume":"35","author":"L Wang","year":"2014","unstructured":"Wang L, Meng L, Wang XW et al (2014) Expression of RRM1 and RRM2 as prognostic markers. Tumour Biol 35:1899\u20131906","journal-title":"Tumour Biol"},{"key":"1788_CR37","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1038\/ncb2897","volume":"16","author":"MK Zeman","year":"2014","unstructured":"Zeman MK, Cimprich KA (2014) Causes and consequences of replication stress. Nat Cell Biol 16:2\u20139","journal-title":"Nat Cell Biol"},{"key":"1788_CR38","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1016\/j.gendis.2022.11.022","volume":"11","author":"Z Zuo","year":"2024","unstructured":"Zuo Z, Zhou Z, Chang Y et al (2024) RRM2 regulation and targeting in cancer. Genes Dis 11:218\u2013233","journal-title":"Genes Dis"}],"container-title":["Genes &amp; Genomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13258-026-01788-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s13258-026-01788-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13258-026-01788-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T10:02:21Z","timestamp":1788775341000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s13258-026-01788-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,7]]},"references-count":37,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["1788"],"URL":"https:\/\/doi.org\/10.1007\/s13258-026-01788-2","relation":{},"ISSN":["1976-9571","2092-9293"],"issn-type":[{"value":"1976-9571","type":"print"},{"value":"2092-9293","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,7]]},"assertion":[{"value":"13 April 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was conducted using publicly available, de-identified TCGA data. Therefore, Institutional Review Board approval and informed consent were not required.","order":2,"name":"Ethics","label":"Institutional review board statement","group":{"name":"EthicsHeading","label":"Declarations"}}]}}