دورية أكاديمية
Molecular Profiling of Circulating Tumour Cells Identifies Notch1 as a Principal Regulator in Advanced Non-Small Cell Lung Cancer.
العنوان: | Molecular Profiling of Circulating Tumour Cells Identifies Notch1 as a Principal Regulator in Advanced Non-Small Cell Lung Cancer. |
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المؤلفون: | Mariscal J; Translational Medical Oncology, Health Research Institute of Santiago (IDIS), University Hospital of Santiago (SERGAS), Trav. Choupana s/n 15706 Santiago de Compostela, Spain., Alonso-Nocelo M; Translational Medical Oncology, Health Research Institute of Santiago (IDIS), University Hospital of Santiago (SERGAS), Trav. Choupana s/n 15706 Santiago de Compostela, Spain., Muinelo-Romay L; Translational Medical Oncology, Health Research Institute of Santiago (IDIS), University Hospital of Santiago (SERGAS), Trav. Choupana s/n 15706 Santiago de Compostela, Spain.; Liquid Biopsy Analysis Unit, Health Research Institute of Santiago (IDIS), University Hospital of Santiago (SERGAS), Trav. Choupana s/n 15706 Santiago de Compostela, Spain., Barbazan J; Translational Medical Oncology, Health Research Institute of Santiago (IDIS), University Hospital of Santiago (SERGAS), Trav. Choupana s/n 15706 Santiago de Compostela, Spain., Vieito M; Translational Medical Oncology, Health Research Institute of Santiago (IDIS), University Hospital of Santiago (SERGAS), Trav. Choupana s/n 15706 Santiago de Compostela, Spain., Abalo A; Translational Medical Oncology, Health Research Institute of Santiago (IDIS), University Hospital of Santiago (SERGAS), Trav. Choupana s/n 15706 Santiago de Compostela, Spain.; Liquid Biopsy Analysis Unit, Health Research Institute of Santiago (IDIS), University Hospital of Santiago (SERGAS), Trav. Choupana s/n 15706 Santiago de Compostela, Spain., Gomez-Tato A; School of Mathematics, University of Santiago de Compostela (Campus Vida), C/Lope Gomez de Marzoa s/n 15782 Santiago de Compostela, Spain., Maria de Los Angeles CC; School of Mathematics, University of Santiago de Compostela (Campus Vida), C/Lope Gomez de Marzoa s/n 15782 Santiago de Compostela, Spain., Garcia-Caballero T; Department of Morphological Sciences, School of Medicine, University of Santiago de Compostela, Spain., Rodriguez C; Translational Medical Oncology, Health Research Institute of Santiago (IDIS), University Hospital of Santiago (SERGAS), Trav. Choupana s/n 15706 Santiago de Compostela, Spain., Brozos E; Translational Medical Oncology, Health Research Institute of Santiago (IDIS), University Hospital of Santiago (SERGAS), Trav. Choupana s/n 15706 Santiago de Compostela, Spain., Baron F; Translational Medical Oncology, Health Research Institute of Santiago (IDIS), University Hospital of Santiago (SERGAS), Trav. Choupana s/n 15706 Santiago de Compostela, Spain., Lopez-Lopez R; Translational Medical Oncology, Health Research Institute of Santiago (IDIS), University Hospital of Santiago (SERGAS), Trav. Choupana s/n 15706 Santiago de Compostela, Spain.; Liquid Biopsy Analysis Unit, Health Research Institute of Santiago (IDIS), University Hospital of Santiago (SERGAS), Trav. Choupana s/n 15706 Santiago de Compostela, Spain., Abal M; Translational Medical Oncology, Health Research Institute of Santiago (IDIS), University Hospital of Santiago (SERGAS), Trav. Choupana s/n 15706 Santiago de Compostela, Spain. |
المصدر: | Scientific reports [Sci Rep] 2016 Nov 30; Vol. 6, pp. 37820. Date of Electronic Publication: 2016 Nov 30. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: London : Nature Publishing Group, copyright 2011- |
مواضيع طبية MeSH: | Carcinoma, Non-Small-Cell Lung/*metabolism , Lung Neoplasms/*metabolism , Neoplastic Cells, Circulating/*metabolism , Receptor, Notch1/*metabolism, A549 Cells ; Aged ; Biomarkers, Tumor/metabolism ; Carcinoma, Non-Small-Cell Lung/pathology ; Cell Line, Tumor ; Disease-Free Survival ; Epithelial Cell Adhesion Molecule/metabolism ; Female ; Humans ; Lung Neoplasms/pathology ; MAP Kinase Signaling System/physiology ; Male ; Middle Aged ; NF-kappa B/metabolism ; Neoplasm Proteins/metabolism ; Neoplastic Cells, Circulating/pathology ; Phosphatidylinositol 3-Kinases/metabolism ; Prognosis ; Signal Transduction/physiology |
مستخلص: | Knowledge on the molecular mechanisms underlying metastasis colonization in Non-Small Cell Lung Cancer (NSCLC) remains incomplete. A complete overview integrating driver mutations, primary tumour heterogeneity and overt metastasis lacks the dynamic contribution of disseminating metastatic cells due to the inaccessibility to the molecular profiling of Circulating Tumour Cells (CTCs). By combining immunoisolation and whole genome amplification, we performed a global gene expression analysis of EpCAM positive CTCs from advanced NSCLC patients. We identified an EpCAM+ CTC-specific expression profile in NSCLC patients mostly associated with cellular movement, cell adhesion and cell-to-cell signalling mediated by PI3K/AKT, ERK1/2 and NF-kB pathways. NOTCH1 emerged as a driver connecting active signalling pathways, with a reduced number of related candidate genes (NOTCH1, PTP4A3, LGALS3 and ITGB3) being further validated by RT-qPCR on an independent cohort of NSCLC patients. In addition, these markers demonstrated high prognostic value for Progression-Free Survival (PFS). In conclusion, molecular characterization of EpCAM+ CTCs from advanced NSCLC patients provided with highly specific biomarkers with potential applicability as a "liquid biopsy" for monitoring of NSCLC patients and confirmed NOTCH1 as a potential therapeutic target to block lung cancer dissemination. |
References: | J Hematol Oncol. 2014 Dec 05;7:87. (PMID: 25477004) Proc Natl Acad Sci U S A. 2009 Dec 29;106(52):22293-8. (PMID: 20007775) Cancer Lett. 2004 Aug 30;212(2):233-9. (PMID: 15279903) J Thorac Oncol. 2012 Feb;7(2):306-15. (PMID: 22173704) Oncotarget. 2016 Apr 5;7(14 ):17905-19. (PMID: 26918447) Int J Cancer. 2014 Jun 1;134(11):2523-33. (PMID: 24122526) Crit Rev Clin Lab Sci. 2014 Jun;51(3):160-71. (PMID: 24641350) Lung Cancer. 2014 Aug;85(2):131-40. (PMID: 24888228) Eur J Cancer. 2013 Apr;49(6):1374-403. (PMID: 23485231) Lung Cancer. 2012 Apr;76(1):19-25. (PMID: 22209049) Sci Rep. 2015 Jul 17;5:12270. (PMID: 26184843) Anticancer Res. 2002 Nov-Dec;22(6A):3117-25. (PMID: 12530054) PLoS One. 2013 Dec 06;8(12):e80458. (PMID: 24324600) Clin Chem. 2013 Jan;59(1):110-8. (PMID: 23014601) J Cell Mol Med. 2012 Oct;16(10):2342-9. (PMID: 22304365) Cancer Lett. 2015 Apr 10;359(2):275-87. (PMID: 25633838) Cell Oncol (Dordr). 2011 Oct;34(5):435-41. (PMID: 21503779) Oncotarget. 2014 Dec 15;5(23):12383-97. (PMID: 25474037) Anticancer Res. 2012 Aug;32(8):3339-44. (PMID: 22843912) Drug Discov Today. 2014 Oct;19(10):1671-6. (PMID: 24928031) Front Biosci (Landmark Ed). 2014 Jun 01;19:896-903. (PMID: 24896324) Onco Targets Ther. 2015 Sep 22;8:2689-97. (PMID: 26445551) Tumour Biol. 2014 Feb;35(2):1211-9. (PMID: 24061641) Nature. 2009 Nov 12;462(7270):182-8. (PMID: 19907488) Eur J Cardiothorac Surg. 2007 May;31(5):783-7. (PMID: 17369045) Int J Cancer. 2011 Oct 1;129(7):1651-60. (PMID: 21128227) Cancers (Basel). 2014 Jan 21;6(1):153-65. (PMID: 24452143) Lung Cancer. 2012 Feb;75(2):242-7. (PMID: 21820198) Br J Cancer. 2011 Oct 25;105(9):1338-41. (PMID: 21970878) Sci Rep. 2015 May 21;5:10338. (PMID: 25996086) J Clin Oncol. 2013 Mar 10;31(8):992-1001. (PMID: 23401443) J Cell Biochem. 2015 Jun;116(6):1019-27. (PMID: 25561332) J Thorac Oncol. 2013 Apr;8(4):398-407. (PMID: 23370366) EPMA J. 2015 Jan 22;6(1):1. (PMID: 25628770) Sci Rep. 2016 Aug 08;6:31086. (PMID: 27499032) Pathology. 2009 Feb;41(2):118-26. (PMID: 19152186) J Natl Cancer Inst. 2005 Dec 21;97(24):1855; author reply 1855-6. (PMID: 16368950) Nature. 2011 May 5;473(7345):101-4. (PMID: 21471965) Biotechnol Adv. 2013 Nov 15;31(7):1063-84. (PMID: 23999357) Expert Opin Investig Drugs. 2013 Feb;22(2):235-44. (PMID: 23176362) PLoS One. 2012;7(7):e40476. (PMID: 22811761) Nat Med. 2014 Aug;20(8):897-903. (PMID: 24880617) CA Cancer J Clin. 2016 Jan-Feb;66(1):7-30. (PMID: 26742998) Br J Cancer. 2006 Jan 16;94(1):128-35. (PMID: 16404366) Nucleic Acids Res. 2012 Jul;40(Web Server issue):W478-83. (PMID: 22573175) Cancer Lett. 2011 Aug 1;307(1):26-36. (PMID: 21463919) Cancer Lett. 2014 Jan 1;342(1):43-51. (PMID: 23981581) Lung Cancer. 2016 Sep;99:102-10. (PMID: 27565922) Semin Oncol. 2014 Feb;41(1):110-25. (PMID: 24565585) |
المشرفين على المادة: | 0 (Biomarkers, Tumor) 0 (Epithelial Cell Adhesion Molecule) 0 (NF-kappa B) 0 (NOTCH1 protein, human) 0 (Neoplasm Proteins) 0 (Receptor, Notch1) EC 2.7.1.- (Phosphatidylinositol 3-Kinases) |
تواريخ الأحداث: | Date Created: 20161201 Date Completed: 20180524 Latest Revision: 20220321 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC5129014 |
DOI: | 10.1038/srep37820 |
PMID: | 27901069 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2045-2322 |
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DOI: | 10.1038/srep37820 |