Methylation of MYLK3 gene promoter region: a biomarker to stratify surgical care in ovarian cancer in a multicentre study
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...
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| Veröffentlicht in: | British journal of cancer 2017-05, Vol.116 (10), p.1287-1293 |
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| creator | Phelps, David L Borley, Jane V Flower, Kirsty J Dina, Roberto Darb-Esfahani, Silvia Braicu, Ioana Sehouli, Jalid Fotopoulou, Christina Wilhelm-Benartzi, Charlotte S Gabra, Hani Yazbek, Joseph Chatterjee, Jayanta Ip, Jacey Khan, Harun Likos-Corbett, Marina-Therese Brown, Robert Ghaem-Maghami, Sadaf |
| description | 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. |
| doi_str_mv | 10.1038/bjc.2017.83 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5482730</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>4322269895</sourcerecordid><originalsourceid>FETCH-LOGICAL-c479t-c8ab22e63fab4e5a90e82a786878d1f85bf7d9ecda2271ba5bfc811f796a22033</originalsourceid><addsrcrecordid>eNqFkctv1DAQxi0EotvCiTuyxAUJsvixiScckFDFS2zFBQ6cLMdxUi9JvNhOpfz3nWVLVRASJ2tmfv7m8RHyhLM1ZxJeNTu7FoyrNch7ZMVLKQoOQt0nK8aYKlgt2Ak5TWmHYc1APSQnAmTJFFQrsly4fLkMJvsw0dDRi-_bz5L2bnJ0H8MYsos0uh6rr6mhjQ-jiT8wlwNNOeK3bqFpjr23ZqDWREc96lyZ6M2E8WSRxYyh4zxkb92UEUl5bpdH5EFnhuQe37xn5Nv7d1_PPxbbLx8-nb_dFnaj6lxYMI0QrpKdaTauNDVzIAzODgpa3kHZdKqtnW2NEIo3BmMLnHeqrjDDpDwjb466-7kZXftrBDPoffS4yqKD8frPyuQvdR-udLnBK0qGAs9vBGL4ObuU9eiTdcNgJhfmpHmNx6-E5OL_KIBgwJg4qD77C92FOU54CaTqCqTioJB6caRsDClF193OzZk-uK_RfX1wX8Nh1ad3V71lf9uNwMsjkLA09S7eafoPvWu407sV</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1896837187</pqid></control><display><type>article</type><title>Methylation of MYLK3 gene promoter region: a biomarker to stratify surgical care in ovarian cancer in a multicentre study</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><source>Nature Journals Online</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><creator>Phelps, David L ; Borley, Jane V ; Flower, Kirsty J ; Dina, Roberto ; Darb-Esfahani, Silvia ; Braicu, Ioana ; Sehouli, Jalid ; Fotopoulou, Christina ; Wilhelm-Benartzi, Charlotte S ; Gabra, Hani ; Yazbek, Joseph ; Chatterjee, Jayanta ; Ip, Jacey ; Khan, Harun ; Likos-Corbett, Marina-Therese ; Brown, Robert ; Ghaem-Maghami, Sadaf</creator><creatorcontrib>Phelps, David L ; Borley, Jane V ; Flower, Kirsty J ; Dina, Roberto ; Darb-Esfahani, Silvia ; Braicu, Ioana ; Sehouli, Jalid ; Fotopoulou, Christina ; Wilhelm-Benartzi, Charlotte S ; Gabra, Hani ; Yazbek, Joseph ; Chatterjee, Jayanta ; Ip, Jacey ; Khan, Harun ; Likos-Corbett, Marina-Therese ; Brown, Robert ; Ghaem-Maghami, Sadaf</creatorcontrib><description>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.</description><identifier>ISSN: 0007-0920</identifier><identifier>EISSN: 1532-1827</identifier><identifier>DOI: 10.1038/bjc.2017.83</identifier><identifier>PMID: 28350786</identifier><identifier>CODEN: BJCAAI</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/208/176/1988 ; 631/67/1517/1709 ; 692/53/2422 ; Biomarkers, Tumor - genetics ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Carcinoma - genetics ; Carcinoma - surgery ; CpG Islands ; Cytoreduction Surgical Procedures ; DNA Methylation ; Drug Resistance ; Epidemiology ; Fallopian Tube Neoplasms - genetics ; Fallopian Tube Neoplasms - surgery ; Female ; Humans ; Kaplan-Meier Estimate ; Molecular Medicine ; Myosin-Light-Chain Kinase - genetics ; Neoplasm, Residual ; Oncology ; Ovarian cancer ; Ovarian Neoplasms - genetics ; Ovarian Neoplasms - surgery ; Peritoneal Neoplasms - genetics ; Peritoneal Neoplasms - surgery ; Promoter Regions, Genetic ; Proportional Hazards Models ; Risk Assessment - methods ; Survival Rate ; Translational Therapeutics</subject><ispartof>British journal of cancer, 2017-05, Vol.116 (10), p.1287-1293</ispartof><rights>The Author(s) 2017</rights><rights>Copyright Nature Publishing Group May 9, 2017</rights><rights>Copyright © 2017 The Author(s) 2017 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c479t-c8ab22e63fab4e5a90e82a786878d1f85bf7d9ecda2271ba5bfc811f796a22033</citedby><cites>FETCH-LOGICAL-c479t-c8ab22e63fab4e5a90e82a786878d1f85bf7d9ecda2271ba5bfc811f796a22033</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482730/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482730/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,41464,42533,51294,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28350786$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Phelps, David L</creatorcontrib><creatorcontrib>Borley, Jane V</creatorcontrib><creatorcontrib>Flower, Kirsty J</creatorcontrib><creatorcontrib>Dina, Roberto</creatorcontrib><creatorcontrib>Darb-Esfahani, Silvia</creatorcontrib><creatorcontrib>Braicu, Ioana</creatorcontrib><creatorcontrib>Sehouli, Jalid</creatorcontrib><creatorcontrib>Fotopoulou, Christina</creatorcontrib><creatorcontrib>Wilhelm-Benartzi, Charlotte S</creatorcontrib><creatorcontrib>Gabra, Hani</creatorcontrib><creatorcontrib>Yazbek, Joseph</creatorcontrib><creatorcontrib>Chatterjee, Jayanta</creatorcontrib><creatorcontrib>Ip, Jacey</creatorcontrib><creatorcontrib>Khan, Harun</creatorcontrib><creatorcontrib>Likos-Corbett, Marina-Therese</creatorcontrib><creatorcontrib>Brown, Robert</creatorcontrib><creatorcontrib>Ghaem-Maghami, Sadaf</creatorcontrib><title>Methylation of MYLK3 gene promoter region: a biomarker to stratify surgical care in ovarian cancer in a multicentre study</title><title>British journal of cancer</title><addtitle>Br J Cancer</addtitle><addtitle>Br J Cancer</addtitle><description>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.</description><subject>631/208/176/1988</subject><subject>631/67/1517/1709</subject><subject>692/53/2422</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Carcinoma - genetics</subject><subject>Carcinoma - surgery</subject><subject>CpG Islands</subject><subject>Cytoreduction Surgical Procedures</subject><subject>DNA Methylation</subject><subject>Drug Resistance</subject><subject>Epidemiology</subject><subject>Fallopian Tube Neoplasms - genetics</subject><subject>Fallopian Tube Neoplasms - surgery</subject><subject>Female</subject><subject>Humans</subject><subject>Kaplan-Meier Estimate</subject><subject>Molecular Medicine</subject><subject>Myosin-Light-Chain Kinase - genetics</subject><subject>Neoplasm, Residual</subject><subject>Oncology</subject><subject>Ovarian cancer</subject><subject>Ovarian Neoplasms - genetics</subject><subject>Ovarian Neoplasms - surgery</subject><subject>Peritoneal Neoplasms - genetics</subject><subject>Peritoneal Neoplasms - surgery</subject><subject>Promoter Regions, Genetic</subject><subject>Proportional Hazards Models</subject><subject>Risk Assessment - methods</subject><subject>Survival Rate</subject><subject>Translational Therapeutics</subject><issn>0007-0920</issn><issn>1532-1827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkctv1DAQxi0EotvCiTuyxAUJsvixiScckFDFS2zFBQ6cLMdxUi9JvNhOpfz3nWVLVRASJ2tmfv7m8RHyhLM1ZxJeNTu7FoyrNch7ZMVLKQoOQt0nK8aYKlgt2Ak5TWmHYc1APSQnAmTJFFQrsly4fLkMJvsw0dDRi-_bz5L2bnJ0H8MYsos0uh6rr6mhjQ-jiT8wlwNNOeK3bqFpjr23ZqDWREc96lyZ6M2E8WSRxYyh4zxkb92UEUl5bpdH5EFnhuQe37xn5Nv7d1_PPxbbLx8-nb_dFnaj6lxYMI0QrpKdaTauNDVzIAzODgpa3kHZdKqtnW2NEIo3BmMLnHeqrjDDpDwjb466-7kZXftrBDPoffS4yqKD8frPyuQvdR-udLnBK0qGAs9vBGL4ObuU9eiTdcNgJhfmpHmNx6-E5OL_KIBgwJg4qD77C92FOU54CaTqCqTioJB6caRsDClF193OzZk-uK_RfX1wX8Nh1ad3V71lf9uNwMsjkLA09S7eafoPvWu407sV</recordid><startdate>20170509</startdate><enddate>20170509</enddate><creator>Phelps, David L</creator><creator>Borley, Jane V</creator><creator>Flower, Kirsty J</creator><creator>Dina, Roberto</creator><creator>Darb-Esfahani, Silvia</creator><creator>Braicu, Ioana</creator><creator>Sehouli, Jalid</creator><creator>Fotopoulou, Christina</creator><creator>Wilhelm-Benartzi, Charlotte S</creator><creator>Gabra, Hani</creator><creator>Yazbek, Joseph</creator><creator>Chatterjee, Jayanta</creator><creator>Ip, Jacey</creator><creator>Khan, Harun</creator><creator>Likos-Corbett, Marina-Therese</creator><creator>Brown, Robert</creator><creator>Ghaem-Maghami, Sadaf</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>7TM</scope><scope>5PM</scope></search><sort><creationdate>20170509</creationdate><title>Methylation of MYLK3 gene promoter region: a biomarker to stratify surgical care in ovarian cancer in a multicentre study</title><author>Phelps, David L ; Borley, Jane V ; Flower, Kirsty J ; Dina, Roberto ; Darb-Esfahani, Silvia ; Braicu, Ioana ; Sehouli, Jalid ; Fotopoulou, Christina ; Wilhelm-Benartzi, Charlotte S ; Gabra, Hani ; Yazbek, Joseph ; Chatterjee, Jayanta ; Ip, Jacey ; Khan, Harun ; Likos-Corbett, Marina-Therese ; Brown, Robert ; Ghaem-Maghami, Sadaf</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c479t-c8ab22e63fab4e5a90e82a786878d1f85bf7d9ecda2271ba5bfc811f796a22033</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>631/208/176/1988</topic><topic>631/67/1517/1709</topic><topic>692/53/2422</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Carcinoma - genetics</topic><topic>Carcinoma - surgery</topic><topic>CpG Islands</topic><topic>Cytoreduction Surgical Procedures</topic><topic>DNA Methylation</topic><topic>Drug Resistance</topic><topic>Epidemiology</topic><topic>Fallopian Tube Neoplasms - genetics</topic><topic>Fallopian Tube Neoplasms - surgery</topic><topic>Female</topic><topic>Humans</topic><topic>Kaplan-Meier Estimate</topic><topic>Molecular Medicine</topic><topic>Myosin-Light-Chain Kinase - genetics</topic><topic>Neoplasm, Residual</topic><topic>Oncology</topic><topic>Ovarian cancer</topic><topic>Ovarian Neoplasms - genetics</topic><topic>Ovarian Neoplasms - surgery</topic><topic>Peritoneal Neoplasms - genetics</topic><topic>Peritoneal Neoplasms - surgery</topic><topic>Promoter Regions, Genetic</topic><topic>Proportional Hazards Models</topic><topic>Risk Assessment - methods</topic><topic>Survival Rate</topic><topic>Translational Therapeutics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Phelps, David L</creatorcontrib><creatorcontrib>Borley, Jane V</creatorcontrib><creatorcontrib>Flower, Kirsty J</creatorcontrib><creatorcontrib>Dina, Roberto</creatorcontrib><creatorcontrib>Darb-Esfahani, Silvia</creatorcontrib><creatorcontrib>Braicu, Ioana</creatorcontrib><creatorcontrib>Sehouli, Jalid</creatorcontrib><creatorcontrib>Fotopoulou, Christina</creatorcontrib><creatorcontrib>Wilhelm-Benartzi, Charlotte S</creatorcontrib><creatorcontrib>Gabra, Hani</creatorcontrib><creatorcontrib>Yazbek, Joseph</creatorcontrib><creatorcontrib>Chatterjee, Jayanta</creatorcontrib><creatorcontrib>Ip, Jacey</creatorcontrib><creatorcontrib>Khan, Harun</creatorcontrib><creatorcontrib>Likos-Corbett, Marina-Therese</creatorcontrib><creatorcontrib>Brown, Robert</creatorcontrib><creatorcontrib>Ghaem-Maghami, Sadaf</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>Nucleic Acids Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Phelps, David L</au><au>Borley, Jane V</au><au>Flower, Kirsty J</au><au>Dina, Roberto</au><au>Darb-Esfahani, Silvia</au><au>Braicu, Ioana</au><au>Sehouli, Jalid</au><au>Fotopoulou, Christina</au><au>Wilhelm-Benartzi, Charlotte S</au><au>Gabra, Hani</au><au>Yazbek, Joseph</au><au>Chatterjee, Jayanta</au><au>Ip, Jacey</au><au>Khan, Harun</au><au>Likos-Corbett, Marina-Therese</au><au>Brown, Robert</au><au>Ghaem-Maghami, Sadaf</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Methylation of MYLK3 gene promoter region: a biomarker to stratify surgical care in ovarian cancer in a multicentre study</atitle><jtitle>British journal of cancer</jtitle><stitle>Br J Cancer</stitle><addtitle>Br J Cancer</addtitle><date>2017-05-09</date><risdate>2017</risdate><volume>116</volume><issue>10</issue><spage>1287</spage><epage>1293</epage><pages>1287-1293</pages><issn>0007-0920</issn><eissn>1532-1827</eissn><coden>BJCAAI</coden><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 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.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>28350786</pmid><doi>10.1038/bjc.2017.83</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | British journal of cancer, 2017-05, Vol.116 (10), p.1287-1293 |
| issn | 0007-0920 1532-1827 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5482730 |
| source | MEDLINE; Springer Nature - Complete Springer Journals; Nature Journals Online; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | 631/208/176/1988 631/67/1517/1709 692/53/2422 Biomarkers, Tumor - genetics Biomedical and Life Sciences Biomedicine Cancer Research Carcinoma - genetics Carcinoma - surgery CpG Islands Cytoreduction Surgical Procedures DNA Methylation Drug Resistance Epidemiology Fallopian Tube Neoplasms - genetics Fallopian Tube Neoplasms - surgery Female Humans Kaplan-Meier Estimate Molecular Medicine Myosin-Light-Chain Kinase - genetics Neoplasm, Residual Oncology Ovarian cancer Ovarian Neoplasms - genetics Ovarian Neoplasms - surgery Peritoneal Neoplasms - genetics Peritoneal Neoplasms - surgery Promoter Regions, Genetic Proportional Hazards Models Risk Assessment - methods Survival Rate Translational Therapeutics |
| title | Methylation of MYLK3 gene promoter region: a biomarker to stratify surgical care in ovarian cancer in a multicentre study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-09T19%3A32%3A54IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Methylation%20of%20MYLK3%20gene%20promoter%20region:%20a%20biomarker%20to%20stratify%20surgical%20care%20in%20ovarian%20cancer%20in%20a%20multicentre%20study&rft.jtitle=British%20journal%20of%20cancer&rft.au=Phelps,%20David%20L&rft.date=2017-05-09&rft.volume=116&rft.issue=10&rft.spage=1287&rft.epage=1293&rft.pages=1287-1293&rft.issn=0007-0920&rft.eissn=1532-1827&rft.coden=BJCAAI&rft_id=info:doi/10.1038/bjc.2017.83&rft_dat=%3Cproquest_pubme%3E4322269895%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1896837187&rft_id=info:pmid/28350786&rfr_iscdi=true |