Diagnostic values of GHSR DNA methylation pattern in breast cancer
DNA methylation patterns have been recognised as cancer-specific markers with high potential for clinical applications. We aimed at identifying methylation variations that differentiate between breast cancers and other breast tissue entities to establish a signature for diagnosis. Candidate genomic...
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| Veröffentlicht in: | Breast cancer research and treatment 2012-10, Vol.135 (3), p.705-713 |
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| creator | Botla, Sandeep Kumar Gholami, Amin Moghaddas Malekpour, Mahdi Moskalev, Evgeny A. Fallah, Mahdi Jandaghi, Pouria Aghajani, Ali Bondar, Irina S. Omranipour, Ramesh Malekpour, Fatemeh Mohajeri, Abbas Babadi, Azin Jahangiri Sahin, Özgür Bubnov, Vladimir V. Najmabadi, Hossein Hoheisel, Jörg D. Riazalhosseini, Yasser |
| description | DNA methylation patterns have been recognised as cancer-specific markers with high potential for clinical applications. We aimed at identifying methylation variations that differentiate between breast cancers and other breast tissue entities to establish a signature for diagnosis. Candidate genomic loci were analysed in 117 fresh-frozen breast specimens, which included cancer, benign and normal breast tissues from patients as well as material from healthy individuals. A cancer-specific DNA methylation signature was identified by microarray analysis in a test set of samples (
n
= 52,
p
|
| doi_str_mv | 10.1007/s10549-012-2197-z |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_1093451459</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A356447832</galeid><sourcerecordid>A356447832</sourcerecordid><originalsourceid>FETCH-LOGICAL-c599t-c357e3269b7bfa7c05ede121d19de4848882402a2b18ba303092868d526a3a6a3</originalsourceid><addsrcrecordid>eNqNkltrFDEYhoModq3-AG9kQJTeTM1hcrpc29oWioKH65DJZHZTZpI1yQjtr2_G3doDChJCIHneL-93AOA1gocIQv4hIUgbWUOEa4wkr6-fgAWinNQcI_4ULCBivGYCsj3wIqVLCKHkUD4HexgLKTHGC_Dx2OmVDyk7U_3Sw2RTFfrq9Ozb1-r487IabV5fDTq74KuNztlGXzlftdHqlCujvbHxJXjW6yHZV7tzH_z4dPL96Ky--HJ6frS8qA2VMteGUG4JZrLlba-5gdR2FmHUIdnZRjRCCNxArHGLRKsJJFBiwURHMdNEl70PDrZxNzH8LEazGl0ydhi0t2FKCkFJGooaKv8DJTOLISro20foZZiiL4n8pkptKYN31EoPVjnfhxy1mYOqJaGsabgguFCHf6HK6uzoTPC2d-X-geD9PcHa6iGvUximud7pIYi2oIkhpWh7tYlu1PGqmFTzLKjtLKjiV82zoK6L5s0us6kdbfdHcdv8ArzbAToZPfSxtNOlO46RhkHOCoe3XCpPfmXj_RL96_cbbG7GSA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1039012560</pqid></control><display><type>article</type><title>Diagnostic values of GHSR DNA methylation pattern in breast cancer</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><creator>Botla, Sandeep Kumar ; Gholami, Amin Moghaddas ; Malekpour, Mahdi ; Moskalev, Evgeny A. ; Fallah, Mahdi ; Jandaghi, Pouria ; Aghajani, Ali ; Bondar, Irina S. ; Omranipour, Ramesh ; Malekpour, Fatemeh ; Mohajeri, Abbas ; Babadi, Azin Jahangiri ; Sahin, Özgür ; Bubnov, Vladimir V. ; Najmabadi, Hossein ; Hoheisel, Jörg D. ; Riazalhosseini, Yasser</creator><creatorcontrib>Botla, Sandeep Kumar ; Gholami, Amin Moghaddas ; Malekpour, Mahdi ; Moskalev, Evgeny A. ; Fallah, Mahdi ; Jandaghi, Pouria ; Aghajani, Ali ; Bondar, Irina S. ; Omranipour, Ramesh ; Malekpour, Fatemeh ; Mohajeri, Abbas ; Babadi, Azin Jahangiri ; Sahin, Özgür ; Bubnov, Vladimir V. ; Najmabadi, Hossein ; Hoheisel, Jörg D. ; Riazalhosseini, Yasser</creatorcontrib><description>DNA methylation patterns have been recognised as cancer-specific markers with high potential for clinical applications. We aimed at identifying methylation variations that differentiate between breast cancers and other breast tissue entities to establish a signature for diagnosis. Candidate genomic loci were analysed in 117 fresh-frozen breast specimens, which included cancer, benign and normal breast tissues from patients as well as material from healthy individuals. A cancer-specific DNA methylation signature was identified by microarray analysis in a test set of samples (
n
= 52,
p
< 2.1 × 10
−4
) and its performance was assessed through bisulphite pyrosequencing in an independent validation set (
n
= 65,
p
< 1.9 × 10
−7
). The signature is associated with
SFRP2
and
GHSR
genes, and exhibited significant hypermethylation in cancers. Normal-appearing breast tissues from cancer patients were also methylated at these loci but to a markedly lower extent. This occurrence of methylated DNA in normal breast tissue of cancer patients is indicative of an epigenetic field defect. Concerning diagnosis, receiver operating characteristic curves and the corresponding area under the curve (AUC) analysis demonstrated a very high sensitivity and specificity of 89.3 and 100 %, respectively, for the
GHSR
methylation pattern (AUC >0.99). To date, this represents the DNA methylation marker of the highest sensitivity and specificity for breast cancer diagnosis. Functionally, ectopic expression of GHSR in a cell line model reduced breast cancer cell invasion without affecting cell viability upon stimulation of cells with ghrelin. Our data suggest a link between epigenetic down-regulation of GHSR and breast cancer cell invasion.</description><identifier>ISSN: 0167-6806</identifier><identifier>EISSN: 1573-7217</identifier><identifier>DOI: 10.1007/s10549-012-2197-z</identifier><identifier>PMID: 22899222</identifier><identifier>CODEN: BCTRD6</identifier><language>eng</language><publisher>Boston: Springer US</publisher><subject>Benign ; Biological and medical sciences ; Biomarkers, Tumor - analysis ; Biomarkers, Tumor - genetics ; Breast cancer ; Breast Neoplasms - diagnosis ; Breast Neoplasms - genetics ; Breast Neoplasms - pathology ; Cancer ; Cancer research ; Cancer therapies ; Cell culture ; Cell Line, Tumor ; CpG Islands ; Data processing ; Diagnosis ; DNA ; DNA Methylation ; DNA microarrays ; Down-Regulation ; Epigenesis, Genetic ; Epigenetics ; Female ; Gene Expression Regulation, Neoplastic ; Genes ; Genetic aspects ; genomics ; ghrelin ; Gynecology. Andrology. Obstetrics ; Humans ; Mammary gland diseases ; Medical diagnosis ; Medical sciences ; Medicine ; Medicine & Public Health ; Membrane Proteins - genetics ; Methylation ; Microarray Analysis ; Oncology ; Preclinical Study ; Predictive Value of Tests ; Receptors, Ghrelin - genetics ; Receptors, Ghrelin - metabolism ; Reference Values ; Reproducibility of Results ; ROC Curve ; Sensitivity and Specificity ; Therapeutic applications ; Tumors</subject><ispartof>Breast cancer research and treatment, 2012-10, Vol.135 (3), p.705-713</ispartof><rights>Springer Science+Business Media, LLC. 2012</rights><rights>2015 INIST-CNRS</rights><rights>COPYRIGHT 2012 Springer</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c599t-c357e3269b7bfa7c05ede121d19de4848882402a2b18ba303092868d526a3a6a3</citedby><cites>FETCH-LOGICAL-c599t-c357e3269b7bfa7c05ede121d19de4848882402a2b18ba303092868d526a3a6a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10549-012-2197-z$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10549-012-2197-z$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27903,27904,41467,42536,51297</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26346076$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22899222$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Botla, Sandeep Kumar</creatorcontrib><creatorcontrib>Gholami, Amin Moghaddas</creatorcontrib><creatorcontrib>Malekpour, Mahdi</creatorcontrib><creatorcontrib>Moskalev, Evgeny A.</creatorcontrib><creatorcontrib>Fallah, Mahdi</creatorcontrib><creatorcontrib>Jandaghi, Pouria</creatorcontrib><creatorcontrib>Aghajani, Ali</creatorcontrib><creatorcontrib>Bondar, Irina S.</creatorcontrib><creatorcontrib>Omranipour, Ramesh</creatorcontrib><creatorcontrib>Malekpour, Fatemeh</creatorcontrib><creatorcontrib>Mohajeri, Abbas</creatorcontrib><creatorcontrib>Babadi, Azin Jahangiri</creatorcontrib><creatorcontrib>Sahin, Özgür</creatorcontrib><creatorcontrib>Bubnov, Vladimir V.</creatorcontrib><creatorcontrib>Najmabadi, Hossein</creatorcontrib><creatorcontrib>Hoheisel, Jörg D.</creatorcontrib><creatorcontrib>Riazalhosseini, Yasser</creatorcontrib><title>Diagnostic values of GHSR DNA methylation pattern in breast cancer</title><title>Breast cancer research and treatment</title><addtitle>Breast Cancer Res Treat</addtitle><addtitle>Breast Cancer Res Treat</addtitle><description>DNA methylation patterns have been recognised as cancer-specific markers with high potential for clinical applications. We aimed at identifying methylation variations that differentiate between breast cancers and other breast tissue entities to establish a signature for diagnosis. Candidate genomic loci were analysed in 117 fresh-frozen breast specimens, which included cancer, benign and normal breast tissues from patients as well as material from healthy individuals. A cancer-specific DNA methylation signature was identified by microarray analysis in a test set of samples (
n
= 52,
p
< 2.1 × 10
−4
) and its performance was assessed through bisulphite pyrosequencing in an independent validation set (
n
= 65,
p
< 1.9 × 10
−7
). The signature is associated with
SFRP2
and
GHSR
genes, and exhibited significant hypermethylation in cancers. Normal-appearing breast tissues from cancer patients were also methylated at these loci but to a markedly lower extent. This occurrence of methylated DNA in normal breast tissue of cancer patients is indicative of an epigenetic field defect. Concerning diagnosis, receiver operating characteristic curves and the corresponding area under the curve (AUC) analysis demonstrated a very high sensitivity and specificity of 89.3 and 100 %, respectively, for the
GHSR
methylation pattern (AUC >0.99). To date, this represents the DNA methylation marker of the highest sensitivity and specificity for breast cancer diagnosis. Functionally, ectopic expression of GHSR in a cell line model reduced breast cancer cell invasion without affecting cell viability upon stimulation of cells with ghrelin. Our data suggest a link between epigenetic down-regulation of GHSR and breast cancer cell invasion.</description><subject>Benign</subject><subject>Biological and medical sciences</subject><subject>Biomarkers, Tumor - analysis</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - diagnosis</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - pathology</subject><subject>Cancer</subject><subject>Cancer research</subject><subject>Cancer therapies</subject><subject>Cell culture</subject><subject>Cell Line, Tumor</subject><subject>CpG Islands</subject><subject>Data processing</subject><subject>Diagnosis</subject><subject>DNA</subject><subject>DNA Methylation</subject><subject>DNA microarrays</subject><subject>Down-Regulation</subject><subject>Epigenesis, Genetic</subject><subject>Epigenetics</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>genomics</subject><subject>ghrelin</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>Mammary gland diseases</subject><subject>Medical diagnosis</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Membrane Proteins - genetics</subject><subject>Methylation</subject><subject>Microarray Analysis</subject><subject>Oncology</subject><subject>Preclinical Study</subject><subject>Predictive Value of Tests</subject><subject>Receptors, Ghrelin - genetics</subject><subject>Receptors, Ghrelin - metabolism</subject><subject>Reference Values</subject><subject>Reproducibility of Results</subject><subject>ROC Curve</subject><subject>Sensitivity and Specificity</subject><subject>Therapeutic applications</subject><subject>Tumors</subject><issn>0167-6806</issn><issn>1573-7217</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqNkltrFDEYhoModq3-AG9kQJTeTM1hcrpc29oWioKH65DJZHZTZpI1yQjtr2_G3doDChJCIHneL-93AOA1gocIQv4hIUgbWUOEa4wkr6-fgAWinNQcI_4ULCBivGYCsj3wIqVLCKHkUD4HexgLKTHGC_Dx2OmVDyk7U_3Sw2RTFfrq9Ozb1-r487IabV5fDTq74KuNztlGXzlftdHqlCujvbHxJXjW6yHZV7tzH_z4dPL96Ky--HJ6frS8qA2VMteGUG4JZrLlba-5gdR2FmHUIdnZRjRCCNxArHGLRKsJJFBiwURHMdNEl70PDrZxNzH8LEazGl0ydhi0t2FKCkFJGooaKv8DJTOLISro20foZZiiL4n8pkptKYN31EoPVjnfhxy1mYOqJaGsabgguFCHf6HK6uzoTPC2d-X-geD9PcHa6iGvUximud7pIYi2oIkhpWh7tYlu1PGqmFTzLKjtLKjiV82zoK6L5s0us6kdbfdHcdv8ArzbAToZPfSxtNOlO46RhkHOCoe3XCpPfmXj_RL96_cbbG7GSA</recordid><startdate>20121001</startdate><enddate>20121001</enddate><creator>Botla, Sandeep Kumar</creator><creator>Gholami, Amin Moghaddas</creator><creator>Malekpour, Mahdi</creator><creator>Moskalev, Evgeny A.</creator><creator>Fallah, Mahdi</creator><creator>Jandaghi, Pouria</creator><creator>Aghajani, Ali</creator><creator>Bondar, Irina S.</creator><creator>Omranipour, Ramesh</creator><creator>Malekpour, Fatemeh</creator><creator>Mohajeri, Abbas</creator><creator>Babadi, Azin Jahangiri</creator><creator>Sahin, Özgür</creator><creator>Bubnov, Vladimir V.</creator><creator>Najmabadi, Hossein</creator><creator>Hoheisel, Jörg D.</creator><creator>Riazalhosseini, Yasser</creator><general>Springer US</general><general>Springer</general><general>Springer Nature B.V</general><scope>IQODW</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>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>K9-</scope><scope>K9.</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>7TM</scope></search><sort><creationdate>20121001</creationdate><title>Diagnostic values of GHSR DNA methylation pattern in breast cancer</title><author>Botla, Sandeep Kumar ; Gholami, Amin Moghaddas ; Malekpour, Mahdi ; Moskalev, Evgeny A. ; Fallah, Mahdi ; Jandaghi, Pouria ; Aghajani, Ali ; Bondar, Irina S. ; Omranipour, Ramesh ; Malekpour, Fatemeh ; Mohajeri, Abbas ; Babadi, Azin Jahangiri ; Sahin, Özgür ; Bubnov, Vladimir V. ; Najmabadi, Hossein ; Hoheisel, Jörg D. ; Riazalhosseini, Yasser</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c599t-c357e3269b7bfa7c05ede121d19de4848882402a2b18ba303092868d526a3a6a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Benign</topic><topic>Biological and medical sciences</topic><topic>Biomarkers, Tumor - analysis</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - diagnosis</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - pathology</topic><topic>Cancer</topic><topic>Cancer research</topic><topic>Cancer therapies</topic><topic>Cell culture</topic><topic>Cell Line, Tumor</topic><topic>CpG Islands</topic><topic>Data processing</topic><topic>Diagnosis</topic><topic>DNA</topic><topic>DNA Methylation</topic><topic>DNA microarrays</topic><topic>Down-Regulation</topic><topic>Epigenesis, Genetic</topic><topic>Epigenetics</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>genomics</topic><topic>ghrelin</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>Mammary gland diseases</topic><topic>Medical diagnosis</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Membrane Proteins - genetics</topic><topic>Methylation</topic><topic>Microarray Analysis</topic><topic>Oncology</topic><topic>Preclinical Study</topic><topic>Predictive Value of Tests</topic><topic>Receptors, Ghrelin - genetics</topic><topic>Receptors, Ghrelin - metabolism</topic><topic>Reference Values</topic><topic>Reproducibility of Results</topic><topic>ROC Curve</topic><topic>Sensitivity and Specificity</topic><topic>Therapeutic applications</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Botla, Sandeep Kumar</creatorcontrib><creatorcontrib>Gholami, Amin Moghaddas</creatorcontrib><creatorcontrib>Malekpour, Mahdi</creatorcontrib><creatorcontrib>Moskalev, Evgeny A.</creatorcontrib><creatorcontrib>Fallah, Mahdi</creatorcontrib><creatorcontrib>Jandaghi, Pouria</creatorcontrib><creatorcontrib>Aghajani, Ali</creatorcontrib><creatorcontrib>Bondar, Irina S.</creatorcontrib><creatorcontrib>Omranipour, Ramesh</creatorcontrib><creatorcontrib>Malekpour, Fatemeh</creatorcontrib><creatorcontrib>Mohajeri, Abbas</creatorcontrib><creatorcontrib>Babadi, Azin Jahangiri</creatorcontrib><creatorcontrib>Sahin, Özgür</creatorcontrib><creatorcontrib>Bubnov, Vladimir V.</creatorcontrib><creatorcontrib>Najmabadi, Hossein</creatorcontrib><creatorcontrib>Hoheisel, Jörg D.</creatorcontrib><creatorcontrib>Riazalhosseini, Yasser</creatorcontrib><collection>Pascal-Francis</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>Oncogenes and Growth Factors 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>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</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>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</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 Basic</collection><collection>MEDLINE - Academic</collection><collection>Nucleic Acids Abstracts</collection><jtitle>Breast cancer research and treatment</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Botla, Sandeep Kumar</au><au>Gholami, Amin Moghaddas</au><au>Malekpour, Mahdi</au><au>Moskalev, Evgeny A.</au><au>Fallah, Mahdi</au><au>Jandaghi, Pouria</au><au>Aghajani, Ali</au><au>Bondar, Irina S.</au><au>Omranipour, Ramesh</au><au>Malekpour, Fatemeh</au><au>Mohajeri, Abbas</au><au>Babadi, Azin Jahangiri</au><au>Sahin, Özgür</au><au>Bubnov, Vladimir V.</au><au>Najmabadi, Hossein</au><au>Hoheisel, Jörg D.</au><au>Riazalhosseini, Yasser</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Diagnostic values of GHSR DNA methylation pattern in breast cancer</atitle><jtitle>Breast cancer research and treatment</jtitle><stitle>Breast Cancer Res Treat</stitle><addtitle>Breast Cancer Res Treat</addtitle><date>2012-10-01</date><risdate>2012</risdate><volume>135</volume><issue>3</issue><spage>705</spage><epage>713</epage><pages>705-713</pages><issn>0167-6806</issn><eissn>1573-7217</eissn><coden>BCTRD6</coden><abstract>DNA methylation patterns have been recognised as cancer-specific markers with high potential for clinical applications. We aimed at identifying methylation variations that differentiate between breast cancers and other breast tissue entities to establish a signature for diagnosis. Candidate genomic loci were analysed in 117 fresh-frozen breast specimens, which included cancer, benign and normal breast tissues from patients as well as material from healthy individuals. A cancer-specific DNA methylation signature was identified by microarray analysis in a test set of samples (
n
= 52,
p
< 2.1 × 10
−4
) and its performance was assessed through bisulphite pyrosequencing in an independent validation set (
n
= 65,
p
< 1.9 × 10
−7
). The signature is associated with
SFRP2
and
GHSR
genes, and exhibited significant hypermethylation in cancers. Normal-appearing breast tissues from cancer patients were also methylated at these loci but to a markedly lower extent. This occurrence of methylated DNA in normal breast tissue of cancer patients is indicative of an epigenetic field defect. Concerning diagnosis, receiver operating characteristic curves and the corresponding area under the curve (AUC) analysis demonstrated a very high sensitivity and specificity of 89.3 and 100 %, respectively, for the
GHSR
methylation pattern (AUC >0.99). To date, this represents the DNA methylation marker of the highest sensitivity and specificity for breast cancer diagnosis. Functionally, ectopic expression of GHSR in a cell line model reduced breast cancer cell invasion without affecting cell viability upon stimulation of cells with ghrelin. Our data suggest a link between epigenetic down-regulation of GHSR and breast cancer cell invasion.</abstract><cop>Boston</cop><pub>Springer US</pub><pmid>22899222</pmid><doi>10.1007/s10549-012-2197-z</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0167-6806 |
| ispartof | Breast cancer research and treatment, 2012-10, Vol.135 (3), p.705-713 |
| issn | 0167-6806 1573-7217 |
| language | eng |
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| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | Benign Biological and medical sciences Biomarkers, Tumor - analysis Biomarkers, Tumor - genetics Breast cancer Breast Neoplasms - diagnosis Breast Neoplasms - genetics Breast Neoplasms - pathology Cancer Cancer research Cancer therapies Cell culture Cell Line, Tumor CpG Islands Data processing Diagnosis DNA DNA Methylation DNA microarrays Down-Regulation Epigenesis, Genetic Epigenetics Female Gene Expression Regulation, Neoplastic Genes Genetic aspects genomics ghrelin Gynecology. Andrology. Obstetrics Humans Mammary gland diseases Medical diagnosis Medical sciences Medicine Medicine & Public Health Membrane Proteins - genetics Methylation Microarray Analysis Oncology Preclinical Study Predictive Value of Tests Receptors, Ghrelin - genetics Receptors, Ghrelin - metabolism Reference Values Reproducibility of Results ROC Curve Sensitivity and Specificity Therapeutic applications Tumors |
| title | Diagnostic values of GHSR DNA methylation pattern in breast cancer |
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