Methylation of MYLK3 gene promoter region: a biomarker to stratify surgical care in ovarian cancer in a multi-centre study

File Description SizeFormat 
bjc201783a.pdfPublished version1.6 MBAdobe PDFDownload
Title: Methylation of MYLK3 gene promoter region: a biomarker to stratify surgical care in ovarian cancer in a multi-centre study
Author(s): Phelps, DL
Borley, J
Flower, K
Dina, R
Darb-Esfahani, S
Braicu, I
Sehouli, J
Fotopoulou, C
Wilhelm-Benartzi, CS
Gabra, H
Yazbek, J
Chatterjee, J
Ip, J
Khan, H
Likos-Corbett, MT
Brown, R
Ghaem-Maghami, S
Item Type: Journal Article
Abstract: 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 was 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 dataset. Kaplan-Meier curves and Cox models tested survival. Results Altogether 803 women with serous ovarian cancer were studied. No RD was associated with significantly improved overall- (OS) (hazard ratio [HR] 1.25, 95% CI 1.06-1.47; P=0.0076) and progression-free survival (PFS) (HR 1.23, 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, 0.31-0.84; P=0.01), Charité (0.46, 0.21-1.01; P=0.05), TCGA (0.64, 0.44-0.93; P=0.02)). Conclusion MYLK3 methylation is associated with improved OS in patients with the least RD, which could potentially be used to determine response to surgery.
Publication Date: 28-Mar-2017
Date of Acceptance: 3-Mar-2017
URI: http://hdl.handle.net/10044/1/45456
DOI: https://dx.doi.org/10.1038/bjc.2017.83
ISSN: 1532-1827
Publisher: Cancer Research UK
Start Page: 1287
End Page: 1293
Journal / Book Title: British Journal of Cancer
Volume: 116
Sponsor/Funder: Cancer Research UK
Imperial College Healthcare NHS Trust- BRC Funding
Cancer Research UK
Imperial College Healthcare NHS Trust- BRC Funding
Imperial College Healthcare NHS Trust- BRC Funding
Funder's Grant Number: C536/A13086
RD205
C17375/A16989
RDB01 79560
RDB04 79560
Copyright Statement: © 2017 The Author(s). This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
ovarian cancer
surgery
biomarker
MYLK3
cg13247990
DNA methylation
CpG
PROGRESSION-FREE SURVIVAL
LIGHT-CHAIN KINASE
DNA METHYLATION
SURGERY
GLIOBLASTOMA
CHEMOTHERAPY
TEMOZOLOMIDE
Biomarkers, Tumor
Carcinoma
CpG Islands
Cytoreduction Surgical Procedures
DNA Methylation
Fallopian Tube Neoplasms
Female
Humans
Kaplan-Meier Estimate
Myosin-Light-Chain Kinase
Neoplasm, Residual
Ovarian Neoplasms
Peritoneal Neoplasms
Promoter Regions, Genetic
Proportional Hazards Models
Risk Assessment
Survival Rate
Humans
Carcinoma
Peritoneal Neoplasms
Ovarian Neoplasms
Fallopian Tube Neoplasms
Neoplasm, Residual
Myosin-Light-Chain Kinase
Survival Rate
Proportional Hazards Models
Risk Assessment
DNA Methylation
CpG Islands
Female
Promoter Regions, Genetic
Kaplan-Meier Estimate
Cytoreduction Surgical Procedures
Biomarkers, Tumor
1112 Oncology And Carcinogenesis
Oncology & Carcinogenesis
Publication Status: Published
Appears in Collections:Division of Surgery
Division of Cancer
Department of Medicine
Faculty of Medicine



Items in Spiral are protected by copyright, with all rights reserved, unless otherwise indicated.

Creative Commons