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Methylation of MYLK3 gene promoter region: a biomarker to stratify surgical care in ovarian cancer in a multicentre study.

التفاصيل البيبلوغرافية
العنوان: Methylation of MYLK3 gene promoter region: a biomarker to stratify surgical care in ovarian cancer in a multicentre study.
المؤلفون: Phelps DL; Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK., Borley JV; Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK., Flower KJ; Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK., Dina R; Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK., Darb-Esfahani S; Institute of Pathology, Charité Universitätsmedizin, Berlin 10117, Germany., Braicu I; Department of Gynaecology, Virchow Campus, Universitätsmedizin, Berlin, Germany., Sehouli J; Department of Gynaecology, Virchow Campus, Universitätsmedizin, Berlin, Germany., Fotopoulou C; Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.; Department of Gynaecology, Virchow Campus, Universitätsmedizin, Berlin, Germany., Wilhelm-Benartzi CS; Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK., Gabra H; Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK., Yazbek J; Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK., Chatterjee J; Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK., Ip J; Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK., Khan H; Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK., Likos-Corbett MT; Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK., Brown R; Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK., Ghaem-Maghami S; Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
المصدر: British journal of cancer [Br J Cancer] 2017 May 09; Vol. 116 (10), pp. 1287-1293. Date of Electronic Publication: 2017 Mar 28.
نوع المنشور: Journal Article; Multicenter Study
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group on behalf of Cancer Research UK Country of Publication: England NLM ID: 0370635 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-1827 (Electronic) Linking ISSN: 00070920 NLM ISO Abbreviation: Br J Cancer Subsets: MEDLINE
أسماء مطبوعة: Publication: 2002- : London : Nature Publishing Group on behalf of Cancer Research UK
Original Publication: London, Lewis.
مواضيع طبية MeSH: Promoter Regions, Genetic*, Carcinoma/*genetics , Fallopian Tube Neoplasms/*genetics , Myosin-Light-Chain Kinase/*genetics , Ovarian Neoplasms/*genetics , Peritoneal Neoplasms/*genetics, Biomarkers, Tumor/genetics ; Carcinoma/surgery ; CpG Islands ; Cytoreduction Surgical Procedures ; DNA Methylation ; Fallopian Tube Neoplasms/surgery ; Female ; Humans ; Kaplan-Meier Estimate ; Neoplasm, Residual ; Ovarian Neoplasms/surgery ; Peritoneal Neoplasms/surgery ; Proportional Hazards Models ; Risk Assessment/methods ; Survival Rate
مستخلص: Background: Survival benefit from surgical debulking of ovarian cancer (OC) is well established, but some women, despite total macroscopic clearance of disease, still have poor prognosis. We aimed to identify biomarkers to predict benefit from conventional surgery.
Methods: Clinical data from women debulked for high-stage OC were analysed (Hammersmith Hospital, London, UK; 2001-2014). Infinium's HumanMethylation27 array interrogated tumour DNA for differentially methylated CpG sites, correlated to survival, in patients with the least residual disease (RD; Hammersmith Array). Validation was performed using bisulphite pyrosequencing (Charité Hospital, Berlin, Germany cohort) and The Cancer Genome Atlas' (TCGA) methylation data set. Kaplan-Meier curves and Cox models tested survival.
Results: Altogether 803 women with serous OC were studied. No RD was associated with significantly improved overall survival (OS; hazard ratio (HR) 1.25, 95% CI 1.06-1.47; P=0.0076) and progression-free survival (PFS; HR 1.23, 95% CI 1.05-1.43; P=0.012; Hammersmith database n=430). Differentially methylated loci within FGF4, FGF21, MYLK2, MYLK3, MYL7, and ITGAE associated with survival. Patients with the least RD had significantly better OS with higher methylation of MYLK3 (Hammersmith (HR 0.51, 95% CI 0.31-0.84; P=0.01), Charité (HR 0.46, 95% CI 0.21-1.01; P=0.05), and TCGA (HR 0.64, 95% CI 0.44-0.93; P=0.02)).
Conclusions: MYLK3 methylation is associated with improved OS in patients with the least RD, which could potentially be used to determine response to surgery.
References: J Immunol. 2008 Apr 15;180(8):5653-61. (PMID: 18390750)
J Natl Cancer Inst. 2015 Nov 27;108(5):. (PMID: 26615020)
Ann Oncol. 2013 Nov;24(11):2813-8. (PMID: 24114859)
Clin Epigenetics. 2015 Jan 14;7:1. (PMID: 25628764)
Ann Surg Oncol. 2010 Jun;17(6):1642-8. (PMID: 20165986)
Sci Transl Med. 2014 Feb 19;6(224):224ra24. (PMID: 24553385)
Int J Gynecol Cancer. 2013 Jan;23(1):25-33. (PMID: 23221605)
Dis Markers. 2012;32(3):195-202. (PMID: 22377736)
Cancer Res. 2014 Jun 1;74(11):3084-91. (PMID: 24728075)
Clin Chim Acta. 2013 Oct 21;425:169-75. (PMID: 23911908)
Br J Cancer. 2012 Sep 25;107(7):1069-74. (PMID: 22935582)
J Gynecol Oncol. 2010 Jun;21(2):75-80. (PMID: 20613895)
Lancet Oncol. 2012 Sep;13(9):916-26. (PMID: 22877848)
Nat Rev Cancer. 2003 Jul;3(7):502-16. (PMID: 12835670)
Clin Cancer Res. 2013 Oct 15;19(20):5788-97. (PMID: 23965899)
J Cell Sci. 2006 Jun 1;119(Pt 11):2269-81. (PMID: 16723733)
Int J Cancer. 2008 Aug 1;123(3):725-9. (PMID: 18478570)
Nature. 2011 Jun 29;474(7353):609-15. (PMID: 21720365)
N Engl J Med. 2010 Sep 2;363(10):943-53. (PMID: 20818904)
FASEB J. 2011 Jul;25(7):2305-12. (PMID: 21441351)
Clin Cancer Res. 2011 Jun 15;17(12):4052-62. (PMID: 21459799)
Gynecol Oncol. 2009 Jul;114(1):26-31. (PMID: 19395008)
BJOG. 2008 Jun;115(7):808-10. (PMID: 18485155)
Clin Cancer Res. 2008 Aug 15;14(16):5198-208. (PMID: 18698038)
Best Pract Res Clin Obstet Gynaecol. 2006 Apr;20(2):207-25. (PMID: 16359925)
Gynecol Oncol. 2013 Feb;128(2):391-6. (PMID: 23142075)
N Engl J Med. 2005 Mar 10;352(10 ):997-1003. (PMID: 15758010)
BMC Genomics. 2014 Mar 26;15:119. (PMID: 24669864)
Circ Res. 2008 Mar 14;102(5):571-80. (PMID: 18202317)
معلومات مُعتمدة: 13086 United Kingdom CRUK_ Cancer Research UK; 15954 United Kingdom CRUK_ Cancer Research UK
المشرفين على المادة: 0 (Biomarkers, Tumor)
EC 2.7.11.18 (Myosin-Light-Chain Kinase)
EC 2.7.11.18 (cardiac myosin light chain kinase, human)
تواريخ الأحداث: Date Created: 20170329 Date Completed: 20170809 Latest Revision: 20240210
رمز التحديث: 20240210
مُعرف محوري في PubMed: PMC5482730
DOI: 10.1038/bjc.2017.83
PMID: 28350786
قاعدة البيانات: MEDLINE
الوصف
تدمد:1532-1827
DOI:10.1038/bjc.2017.83