{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:40:06Z","timestamp":1791412806407,"version":"4.3.3"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T00:00:00Z","timestamp":1726790400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T00:00:00Z","timestamp":1726790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Br J Cancer"],"published-print":{"date-parts":[[2024,11,16]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Despite advances in diagnosis and treatment in lung cancer, therapies still fail to improve patient management due to resistance mechanisms and relapses. As Cancer stem cells (CSCs) directly contribute to tumor growth and therapeutic resistance, their clinical detection represents a major challenge. However specific and additional CSC markers lack. Thus, our aim was to achieve selective detection of CSCs with specific glycan patterns and assess the CSCs burden to predict the risk of relapse in NSCLC tumors.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>The lung CSCs detection and sorting with a lectin MIX were assessed and compared to CD133 in vitro. Then, its putative role as CSC biomarker was evaluated in vivo and its clinical significance on 221 NSCLC patients.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We showed a significant CSCs enrichment in the MIX+ sorted fraction compared to CD133+ cells and confirmed its high tumorigenic capacity. The MIX prognostic value on the overall survival from early stages patients was validated suggesting its potential for detecting CSCs directly linked to tumor aggressiveness.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>The MIX could be more relevant for detecting and sorting CSCs than CD133. Moreover, its prognosis value could enable clinicians to better classify early-stage patients at high risk of relapse in order to tailor therapeutic decisions.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1038\/s41416-024-02839-9","type":"journal-article","created":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T21:01:31Z","timestamp":1726866091000},"page":"1425-1436","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Comparison of methods for cancer stem cell detection in prognosis of early stages NSCLC"],"prefix":"10.1038","volume":"131","author":[{"given":"Bouta\u00eena","family":"Chandouri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Naves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"May","family":"Yassine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e9a","family":"Ikhlef","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00e9my","family":"Tricard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Chaunavel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeinab","family":"Homayed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Pannequin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Girard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Durand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Carr\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0382-4948","authenticated-orcid":false,"given":"Fabrice","family":"Lallou\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,9,20]]},"reference":[{"key":"2839_CR1","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1038\/nrc3775","volume":"14","author":"Z Chen","year":"2014","unstructured":"Chen Z, Fillmore CM, Hammerman PS, Kim CF, Wong K-K. Non-small-cell lung cancers: a heterogeneous set of diseases. Nat Rev Cancer. 2014;14:535\u201346.","journal-title":"Nat Rev Cancer"},{"key":"2839_CR2","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1038\/sj.bjc.6605821","volume":"103","author":"S Bomken","year":"2010","unstructured":"Bomken S, Fi\u0161er K, Heidenreich O, Vormoor J. Understanding the cancer stem cell. Br J Cancer. 2010;103:439\u201345.","journal-title":"Br J Cancer"},{"key":"2839_CR3","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.613198","volume":"11","author":"V Masciale","year":"2021","unstructured":"Masciale V, Banchelli F, Grisendi G, D\u2019Amico R, Maiorana A, Stefani A, et al. New Perspectives in Different Gene Expression Profiles for Early and Locally Advanced Non-Small Cell Lung Cancer Stem Cells. Front Oncol. 2021;11:613198.","journal-title":"Front Oncol"},{"key":"2839_CR4","doi-asserted-by":"publisher","first-page":"288","DOI":"10.21037\/tlcr.2016.06.07","volume":"5","author":"C Zappa","year":"2016","unstructured":"Zappa C, Mousa SA. Non-small cell lung cancer: current treatment and future advances. Transl Lung Cancer Res. 2016;5:288\u2013300.","journal-title":"Transl Lung Cancer Res"},{"key":"2839_CR5","first-page":"242","volume":"3","author":"H Uramoto","year":"2014","unstructured":"Uramoto H, Tanaka F. Recurrence after surgery in patients with NSCLC. Transl Lung Cancer Res. 2014;3:242\u20139.","journal-title":"Transl Lung Cancer Res"},{"key":"2839_CR6","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1007\/978-3-319-24932-2_4","volume":"890","author":"R Suresh","year":"2016","unstructured":"Suresh R, Ali S, Ahmad A, Philip PA, Sarkar FH. The Role of Cancer Stem Cells in Recurrent and Drug-Resistant Lung Cancer. Adv Exp Med Biol. 2016;890:57\u201374.","journal-title":"Adv Exp Med Biol"},{"key":"2839_CR7","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1007\/7651_2016_326","volume":"1516","author":"NHA Halim","year":"2016","unstructured":"Halim NHA, Zakaria N, Satar NA, Yahaya BH. Isolation and Characterization of Cancer Stem Cells of the Non-Small-Cell Lung Cancer (A549) Cell Line. Methods Mol Biol Clifton NJ. 2016;1516:371\u201388.","journal-title":"Methods Mol Biol Clifton NJ"},{"key":"2839_CR8","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.pmu.2015.03.007","volume":"4","author":"T Miyata","year":"2015","unstructured":"Miyata T, Yoshimatsu T, So T, Oyama T, Uramoto H, Osaki T, et al. Cancer stem cell markers in lung cancer. Pers Med Universe. 2015;4:40\u201345.","journal-title":"Pers Med Universe"},{"key":"2839_CR9","doi-asserted-by":"publisher","first-page":"3797","DOI":"10.21873\/anticanres.12663","volume":"38","author":"A Maiuthed","year":"2018","unstructured":"Maiuthed A, Chantarawong W, Chanvorachote P. Lung Cancer Stem Cells and Cancer Stem Cell-targeting Natural Compounds. Anticancer Res. 2018;38:3797\u2013809.","journal-title":"Anticancer Res"},{"key":"2839_CR10","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.873994","volume":"12","author":"Y Zheng","year":"2022","unstructured":"Zheng Y, Wang L, Yin L, Yao Z, Tong R, Xue J, et al. Lung Cancer Stem Cell Markers as Therapeutic Targets: An Update on Signaling Pathways and Therapies. Front Oncol. 2022;12:873994.","journal-title":"Front Oncol"},{"key":"2839_CR11","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1007\/s00109-008-0357-8","volume":"86","author":"S Bidlingmaier","year":"2008","unstructured":"Bidlingmaier S, Zhu X, Liu B. The utility and limitations of glycosylated human CD133 epitopes in defining cancer stem cells. J Mol Med Berl Ger. 2008;86:1025\u201332.","journal-title":"J Mol Med Berl Ger"},{"key":"2839_CR12","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1158\/0008-5472.CAN-09-1820","volume":"70","author":"K Kemper","year":"2010","unstructured":"Kemper K, Sprick MR, de Bree M, Scopelliti A, Vermeulen L, Hoek M, et al. The AC133 Epitope, but not the CD133 Protein, Is Lost upon Cancer Stem Cell Differentiation. Cancer Res. 2010;70:719\u201329.","journal-title":"Cancer Res"},{"key":"2839_CR13","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.918702","volume":"12","author":"S Blondy","year":"2022","unstructured":"Blondy S, Durand S, Lacroix A, Christou N, Bouchaud C, Peyny M, et al. Detection of Glycosylated Markers From Cancer Stem Cells With ColoSTEM Dx Kit for Earlier Prediction of Colon Cancer Aggressiveness. Front Oncol. 2022;12:918702.","journal-title":"Front Oncol"},{"key":"2839_CR14","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202115343","volume":"14","author":"J Guyon","year":"2022","unstructured":"Guyon J, Fernandez-Moncada I, Larrieu CM, Bouchez CL, Pagano Zottola AC, Galvis J, et al. Lactate dehydrogenases promote glioblastoma growth and invasion via a metabolic symbiosis. EMBO Mol Med. 2022;14:e15343.","journal-title":"EMBO Mol Med"},{"key":"2839_CR15","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.cllc.2019.02.005","volume":"20","author":"J Codony-Servat","year":"2019","unstructured":"Codony-Servat J, Codony-Servat C, Cardona AF, Gim\u00e9nez-Capit\u00e1n A, Drozdowskyj A, Berenguer J, et al. Cancer Stem Cell Biomarkers in EGFR-Mutation\u2013Positive Non\u2013Small-Cell Lung Cancer. Clin Lung Cancer. 2019;20:167\u201377.","journal-title":"Clin Lung Cancer"},{"key":"2839_CR16","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1111\/cas.12830","volume":"107","author":"Y Hirohashi","year":"2016","unstructured":"Hirohashi Y, Torigoe T, Tsukahara T, Kanaseki T, Kochin V, Sato N. Immune responses to human cancer stem\u2010like cells\/cancer\u2010initiating cells. Cancer Sci. 2016;107:12\u201317.","journal-title":"Cancer Sci"},{"key":"2839_CR17","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-020-01671-4","volume":"20","author":"C Zhang","year":"2020","unstructured":"Zhang C, Wang H, Wang X, Zhao C, Wang H. CD44, a marker of cancer stem cells, is positively correlated with PD-L1 expression and immune cells infiltration in lung adenocarcinoma. Cancer Cell Int. 2020;20:583.","journal-title":"Cancer Cell Int"},{"key":"2839_CR18","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1007\/s10555-010-9216-5","volume":"29","author":"JP Sullivan","year":"2010","unstructured":"Sullivan JP, Minna JD, Shay JW. Evidence for self-renewing lung cancer stem cells and their implications in tumor initiation, progression, and targeted therapy. Cancer Metastasis Rev. 2010;29:61\u201372.","journal-title":"Cancer Metastasis Rev"},{"key":"2839_CR19","doi-asserted-by":"publisher","first-page":"3082","DOI":"10.1158\/0008-5472.CAN-16-1633","volume":"77","author":"Y Zhang","year":"2017","unstructured":"Zhang Y, Xu W, Guo H, Zhang Y, He Y, Lee SH, et al. NOTCH1 Signaling Regulates Self-Renewal and Platinum Chemoresistance of Cancer Stem\u2013like Cells in Human Non\u2013Small Cell Lung Cancer. Cancer Res. 2017;77:3082\u201391.","journal-title":"Cancer Res"},{"key":"2839_CR20","doi-asserted-by":"publisher","first-page":"16281","DOI":"10.1073\/pnas.0905653106","volume":"106","author":"G Bertolini","year":"2009","unstructured":"Bertolini G, Roz L, Perego P, Tortoreto M, Fontanella E, Gatti L, et al. Highly tumorigenic lung cancer CD133+ cells display stem-like features and are spared by cisplatin treatment. Proc Natl Acad Sci. 2009;106:16281\u20136.","journal-title":"Proc Natl Acad Sci"},{"key":"2839_CR21","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.1097\/JTO.0000000000000563","volume":"10","author":"M Moro","year":"2015","unstructured":"Moro M, Bertolini G, Pastorino U, Roz L, Sozzi G. Combination Treatment with All-Trans Retinoic Acid Prevents Cisplatin-Induced Enrichment of CD133+ Tumor-Initiating Cells and Reveals Heterogeneity of Cancer Stem Cell Compartment in Lung Cancer. J Thorac Oncol. 2015;10:1027\u201336.","journal-title":"J Thorac Oncol"},{"key":"2839_CR22","doi-asserted-by":"publisher","first-page":"e352","DOI":"10.1038\/cddis.2012.93","volume":"3","author":"S Akunuru","year":"2012","unstructured":"Akunuru S, James Zhai Q, Zheng Y. Non-small cell lung cancer stem\/progenitor cells are enriched in multiple distinct phenotypic subpopulations and exhibit plasticity. Cell Death Dis. 2012;3:e352.","journal-title":"Cell Death Dis"},{"key":"2839_CR23","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1038\/nrc3184","volume":"12","author":"LV Nguyen","year":"2012","unstructured":"Nguyen LV, Vanner R, Dirks P, Eaves CJ. Cancer stem cells: an evolving concept. Nat Rev Cancer. 2012;12:133\u201343.","journal-title":"Nat Rev Cancer"},{"key":"2839_CR24","doi-asserted-by":"publisher","first-page":"1270","DOI":"10.1002\/ijc.28478","volume":"134","author":"DP Freitas","year":"2014","unstructured":"Freitas DP, Teixeira CA, Santos-Silva F, Vasconcelos MH, Almeida GM. Therapy-induced enrichment of putative lung cancer stem-like cells. Int J Cancer. 2014;134:1270\u20138.","journal-title":"Int J Cancer"},{"key":"2839_CR25","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1038\/s41568-018-0056-x","volume":"18","author":"NK Lytle","year":"2018","unstructured":"Lytle NK, Barber AG, Reya T. Stem cell fate in cancer growth, progression and therapy resistance. Nat Rev Cancer. 2018;18:669\u201380.","journal-title":"Nat Rev Cancer"},{"key":"2839_CR26","doi-asserted-by":"publisher","first-page":"950","DOI":"10.1002\/ijc.24822","volume":"126","author":"AV Salnikov","year":"2010","unstructured":"Salnikov AV, Gladkich J, Moldenhauer G, Volm M, Mattern J, Herr I. CD133 is indicative for a resistance phenotype but does not represent a prognostic marker for survival of non-small cell lung cancer patients. Int J Cancer. 2010;126:950\u20138.","journal-title":"Int J Cancer"},{"key":"2839_CR27","doi-asserted-by":"publisher","first-page":"1458","DOI":"10.1007\/s12032-010-9646-5","volume":"28","author":"F Li","year":"2011","unstructured":"Li F, Zeng H, Ying K. The combination of stem cell markers CD133 and ABCG2 predicts relapse in stage I non-small cell lung carcinomas. Med Oncol Northwood Lond Engl. 2011;28:1458\u201362.","journal-title":"Med Oncol Northwood Lond Engl"},{"key":"2839_CR28","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1097\/JTO.0b013e3181c20080","volume":"5","author":"JA Boyd","year":"2010","unstructured":"Boyd JA, Hubbs JL, Kim DW, Hollis D, Marks LB, Kelsey CR. Timing of Local and Distant Failure in Resected Lung Cancer: Implications for Reported Rates of Local Failure. J Thorac Oncol. 2010;5:211\u20134.","journal-title":"J Thorac Oncol"},{"key":"2839_CR29","doi-asserted-by":"publisher","first-page":"29","DOI":"10.33594\/000000340","volume":"55","author":"AA Schegoleva","year":"2021","unstructured":"Schegoleva AA, Khozyainova AA, Fedorov AA, Gerashchenko TS, Rodionov EO, Topolnitsky EB, et al. Prognosis of Different Types of Non-Small Cell Lung Cancer Progression: Current State and Perspectives | Cell Physiol Biochem. Cell Physiol Biochem. 2021;55:29\u201348.","journal-title":"Cell Physiol Biochem"},{"key":"2839_CR30","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1016\/j.neo.2018.06.001","volume":"20","author":"S Barkeer","year":"2018","unstructured":"Barkeer S, Chugh S, Batra SK, Ponnusamy MP. Glycosylation of Cancer Stem Cells: Function in Stemness, Tumorigenesis, and Metastasis. Neoplasia NY N. 2018;20:813\u201325.","journal-title":"Neoplasia NY N"},{"key":"2839_CR31","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1038\/nrc3982","volume":"15","author":"SS Pinho","year":"2015","unstructured":"Pinho SS, Reis CA. Glycosylation in cancer: mechanisms and clinical implications. Nat Rev Cancer. 2015;15:540\u201355.","journal-title":"Nat Rev Cancer"},{"key":"2839_CR32","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1634\/theoncologist.2019-0517","volume":"25","author":"J Lathia","year":"2020","unstructured":"Lathia J, Liu H, Matei D. The Clinical Impact of Cancer Stem Cells. Oncologist. 2020;25:123\u201331.","journal-title":"Oncologist"}],"container-title":["British Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41416-024-02839-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41416-024-02839-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41416-024-02839-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T15:12:53Z","timestamp":1730128373000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41416-024-02839-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,20]]},"references-count":32,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2024,11,16]]}},"alternative-id":["2839"],"URL":"https:\/\/doi.org\/10.1038\/s41416-024-02839-9","relation":{},"ISSN":["0007-0920","1532-1827"],"issn-type":[{"value":"0007-0920","type":"print"},{"value":"1532-1827","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,20]]},"assertion":[{"value":"28 July 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 August 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 August 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 September 2024","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The patients of Lyon University Hospital were collected under broad consent and provided by the Lung Biobank from Hospices Civils de Lyon (agreement Number from CRB-Hospices Civils de Lyon: R4-P1-ST1.1.). The study was performed in accordance with the Declaration of Helsinki. All animal experiments were carried out in accordance with relevant guidelines and regulations and were approved by the French Agriculture and Forestry Ministry (APAFIS number: 2019071709325396 #21596).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}]}}