Methylation analysis of DCC gene in saliva samples is an efficient method for non-invasive detection of superficial hypopharyngeal cancer
Background Advances in upper gastrointestinal endoscopic technology have enabled early detection and treatment of hypopharyngeal cancer. However, in-depth pharyngeal observations require sedation and are invasive. It is important to establish a minimally invasive and simple evaluation method to iden...
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| Veröffentlicht in: | British journal of cancer 2024-06, Vol.130 (10), p.1725-1731 |
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| creator | Hirai, Ryosuke Kinugasa, Hideaki Yamamoto, Shumpei Ako, Soichiro Tsutsumi, Koichiro Abe, Makoto Miyahara, Koji Nakagawa, Masahiro Otsuka, Motoyuki |
| description | Background
Advances in upper gastrointestinal endoscopic technology have enabled early detection and treatment of hypopharyngeal cancer. However, in-depth pharyngeal observations require sedation and are invasive. It is important to establish a minimally invasive and simple evaluation method to identify high-risk patients.
Methods
Eighty-seven patients with superficial hypopharyngeal cancer and 51 healthy controls were recruited. We assessed the methylation status of
DCC
,
PTGDR1
,
EDNRB
, and
ECAD
, in tissue and saliva samples and verified the diagnostic accuracy by methylation analyses of their promoter regions using quantitative methylation-specific PCR.
Results
Significant differences between cancer and their surrounding non-cancerous tissues were observed in the methylation values of
DCC
(
p
= 0.003),
EDNRB
(
p
= 0.001), and
ECAD
(
p
= 0.043). Using receiver operating characteristic analyses of the methylation values in saliva samples,
DCC
showed the highest area under the curve values for the detection of superficial hypopharyngeal cancer (0.917, 95% confidence interval = 0.864–0.970), compared with those for
EDNRB
(0.680) and
ECAD
(0.639). When the cutoff for the methylation values of
DCC
was set at ≥0.163, the sensitivity to detect hypopharyngeal cancer was 82.8% and the specificity was 90.2%.
Conclusions
DCC
methylation in saliva samples could be a non-invasive and efficient tool for early detection of hypopharyngeal cancer in high-risk patients. |
| doi_str_mv | 10.1038/s41416-024-02654-2 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11091138</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3014004472</sourcerecordid><originalsourceid>FETCH-LOGICAL-c426t-d7715c616f5387e81dfdb307fc5a43d0a4fa1a3c79861e16151dec7bad39b0f93</originalsourceid><addsrcrecordid>eNp9kU2P1DAMhiMEYoeFP8ABReLCpRA3adOeEBo-pUVc4BxlUmcmqzQpSTvS_AT-NenOsnwcOESW5ddPbL-EPAX2EhjvXmUBAtqK1aK8thFVfY9soOF1BV0t75MNY0xWrK_ZBXmU83VJe9bJh-SCdw3vZN1tyI_POB9OXs8uBqqD9qfsMo2Wvt1u6R4DUhdo1t4ddQnj5DHTItCBorXOOAwzHQsiDtTGREMMlQtHnd0R6YAzmhtw4eVlwrR2aE8PpylOB51OYY8lNToYTI_JA6t9xie38ZJ8e__u6_ZjdfXlw6ftm6vKiLqdq0FKaEwLrV1XwA4GO-w4k9Y0WvCBaWE1aG5k37WA0EIDAxq50wPvd8z2_JK8PnOnZTfiYMoGSXs1JTeWiVTUTv1dCe6g9vGoAFgPwLtCeHFLSPH7gnlWo8sGvdcB45IVZyAYE0LWRfr8H-l1XFI586pqBGecsxVYn1UmxZwT2rtpgKnVanW2WhWr1Y3VakU_-3OPu5Zf3hYBPwtyKZVLp99__wf7Ewvlt2c</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3054303308</pqid></control><display><type>article</type><title>Methylation analysis of DCC gene in saliva samples is an efficient method for non-invasive detection of superficial hypopharyngeal cancer</title><source>MEDLINE</source><source>Springer Online Journals Complete</source><creator>Hirai, Ryosuke ; Kinugasa, Hideaki ; Yamamoto, Shumpei ; Ako, Soichiro ; Tsutsumi, Koichiro ; Abe, Makoto ; Miyahara, Koji ; Nakagawa, Masahiro ; Otsuka, Motoyuki</creator><creatorcontrib>Hirai, Ryosuke ; Kinugasa, Hideaki ; Yamamoto, Shumpei ; Ako, Soichiro ; Tsutsumi, Koichiro ; Abe, Makoto ; Miyahara, Koji ; Nakagawa, Masahiro ; Otsuka, Motoyuki</creatorcontrib><description>Background
Advances in upper gastrointestinal endoscopic technology have enabled early detection and treatment of hypopharyngeal cancer. However, in-depth pharyngeal observations require sedation and are invasive. It is important to establish a minimally invasive and simple evaluation method to identify high-risk patients.
Methods
Eighty-seven patients with superficial hypopharyngeal cancer and 51 healthy controls were recruited. We assessed the methylation status of
DCC
,
PTGDR1
,
EDNRB
, and
ECAD
, in tissue and saliva samples and verified the diagnostic accuracy by methylation analyses of their promoter regions using quantitative methylation-specific PCR.
Results
Significant differences between cancer and their surrounding non-cancerous tissues were observed in the methylation values of
DCC
(
p
= 0.003),
EDNRB
(
p
= 0.001), and
ECAD
(
p
= 0.043). Using receiver operating characteristic analyses of the methylation values in saliva samples,
DCC
showed the highest area under the curve values for the detection of superficial hypopharyngeal cancer (0.917, 95% confidence interval = 0.864–0.970), compared with those for
EDNRB
(0.680) and
ECAD
(0.639). When the cutoff for the methylation values of
DCC
was set at ≥0.163, the sensitivity to detect hypopharyngeal cancer was 82.8% and the specificity was 90.2%.
Conclusions
DCC
methylation in saliva samples could be a non-invasive and efficient tool for early detection of hypopharyngeal cancer in high-risk patients.</description><identifier>ISSN: 0007-0920</identifier><identifier>ISSN: 1532-1827</identifier><identifier>EISSN: 1532-1827</identifier><identifier>DOI: 10.1038/s41416-024-02654-2</identifier><identifier>PMID: 38538728</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/337/176/1988 ; 631/67/1536/1665/3016 ; 631/67/2322 ; Aged ; Biomarkers, Tumor - genetics ; Biomedical and Life Sciences ; Biomedicine ; Cancer ; Cancer Research ; Case-Control Studies ; DCC gene ; DCC Receptor - genetics ; DNA Methylation ; Drug Resistance ; Early Detection of Cancer - methods ; Epidemiology ; Female ; Genes, DCC - genetics ; Humans ; Hypopharyngeal Neoplasms - diagnosis ; Hypopharyngeal Neoplasms - genetics ; Invasiveness ; Male ; Middle Aged ; Molecular Medicine ; Oncology ; Pharynx ; Promoter Regions, Genetic ; Receptor, Endothelin B - genetics ; Risk groups ; ROC Curve ; Saliva ; Saliva - chemistry ; Throat cancer</subject><ispartof>British journal of cancer, 2024-06, Vol.130 (10), p.1725-1731</ispartof><rights>The Author(s) 2024</rights><rights>2024. The Author(s).</rights><rights>The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c426t-d7715c616f5387e81dfdb307fc5a43d0a4fa1a3c79861e16151dec7bad39b0f93</cites><orcidid>0000-0003-4887-1609 ; 0000-0002-3602-9695</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41416-024-02654-2$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41416-024-02654-2$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,27922,27923,41486,42555,51317</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38538728$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hirai, Ryosuke</creatorcontrib><creatorcontrib>Kinugasa, Hideaki</creatorcontrib><creatorcontrib>Yamamoto, Shumpei</creatorcontrib><creatorcontrib>Ako, Soichiro</creatorcontrib><creatorcontrib>Tsutsumi, Koichiro</creatorcontrib><creatorcontrib>Abe, Makoto</creatorcontrib><creatorcontrib>Miyahara, Koji</creatorcontrib><creatorcontrib>Nakagawa, Masahiro</creatorcontrib><creatorcontrib>Otsuka, Motoyuki</creatorcontrib><title>Methylation analysis of DCC gene in saliva samples is an efficient method for non-invasive detection of superficial hypopharyngeal cancer</title><title>British journal of cancer</title><addtitle>Br J Cancer</addtitle><addtitle>Br J Cancer</addtitle><description>Background
Advances in upper gastrointestinal endoscopic technology have enabled early detection and treatment of hypopharyngeal cancer. However, in-depth pharyngeal observations require sedation and are invasive. It is important to establish a minimally invasive and simple evaluation method to identify high-risk patients.
Methods
Eighty-seven patients with superficial hypopharyngeal cancer and 51 healthy controls were recruited. We assessed the methylation status of
DCC
,
PTGDR1
,
EDNRB
, and
ECAD
, in tissue and saliva samples and verified the diagnostic accuracy by methylation analyses of their promoter regions using quantitative methylation-specific PCR.
Results
Significant differences between cancer and their surrounding non-cancerous tissues were observed in the methylation values of
DCC
(
p
= 0.003),
EDNRB
(
p
= 0.001), and
ECAD
(
p
= 0.043). Using receiver operating characteristic analyses of the methylation values in saliva samples,
DCC
showed the highest area under the curve values for the detection of superficial hypopharyngeal cancer (0.917, 95% confidence interval = 0.864–0.970), compared with those for
EDNRB
(0.680) and
ECAD
(0.639). When the cutoff for the methylation values of
DCC
was set at ≥0.163, the sensitivity to detect hypopharyngeal cancer was 82.8% and the specificity was 90.2%.
Conclusions
DCC
methylation in saliva samples could be a non-invasive and efficient tool for early detection of hypopharyngeal cancer in high-risk patients.</description><subject>631/337/176/1988</subject><subject>631/67/1536/1665/3016</subject><subject>631/67/2322</subject><subject>Aged</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer</subject><subject>Cancer Research</subject><subject>Case-Control Studies</subject><subject>DCC gene</subject><subject>DCC Receptor - genetics</subject><subject>DNA Methylation</subject><subject>Drug Resistance</subject><subject>Early Detection of Cancer - methods</subject><subject>Epidemiology</subject><subject>Female</subject><subject>Genes, DCC - genetics</subject><subject>Humans</subject><subject>Hypopharyngeal Neoplasms - diagnosis</subject><subject>Hypopharyngeal Neoplasms - genetics</subject><subject>Invasiveness</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Molecular Medicine</subject><subject>Oncology</subject><subject>Pharynx</subject><subject>Promoter Regions, Genetic</subject><subject>Receptor, Endothelin B - genetics</subject><subject>Risk groups</subject><subject>ROC Curve</subject><subject>Saliva</subject><subject>Saliva - chemistry</subject><subject>Throat cancer</subject><issn>0007-0920</issn><issn>1532-1827</issn><issn>1532-1827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><recordid>eNp9kU2P1DAMhiMEYoeFP8ABReLCpRA3adOeEBo-pUVc4BxlUmcmqzQpSTvS_AT-NenOsnwcOESW5ddPbL-EPAX2EhjvXmUBAtqK1aK8thFVfY9soOF1BV0t75MNY0xWrK_ZBXmU83VJe9bJh-SCdw3vZN1tyI_POB9OXs8uBqqD9qfsMo2Wvt1u6R4DUhdo1t4ddQnj5DHTItCBorXOOAwzHQsiDtTGREMMlQtHnd0R6YAzmhtw4eVlwrR2aE8PpylOB51OYY8lNToYTI_JA6t9xie38ZJ8e__u6_ZjdfXlw6ftm6vKiLqdq0FKaEwLrV1XwA4GO-w4k9Y0WvCBaWE1aG5k37WA0EIDAxq50wPvd8z2_JK8PnOnZTfiYMoGSXs1JTeWiVTUTv1dCe6g9vGoAFgPwLtCeHFLSPH7gnlWo8sGvdcB45IVZyAYE0LWRfr8H-l1XFI586pqBGecsxVYn1UmxZwT2rtpgKnVanW2WhWr1Y3VakU_-3OPu5Zf3hYBPwtyKZVLp99__wf7Ewvlt2c</recordid><startdate>20240601</startdate><enddate>20240601</enddate><creator>Hirai, Ryosuke</creator><creator>Kinugasa, Hideaki</creator><creator>Yamamoto, Shumpei</creator><creator>Ako, Soichiro</creator><creator>Tsutsumi, Koichiro</creator><creator>Abe, Makoto</creator><creator>Miyahara, Koji</creator><creator>Nakagawa, Masahiro</creator><creator>Otsuka, Motoyuki</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>7TO</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-4887-1609</orcidid><orcidid>https://orcid.org/0000-0002-3602-9695</orcidid></search><sort><creationdate>20240601</creationdate><title>Methylation analysis of DCC gene in saliva samples is an efficient method for non-invasive detection of superficial hypopharyngeal cancer</title><author>Hirai, Ryosuke ; Kinugasa, Hideaki ; Yamamoto, Shumpei ; Ako, Soichiro ; Tsutsumi, Koichiro ; Abe, Makoto ; Miyahara, Koji ; Nakagawa, Masahiro ; Otsuka, Motoyuki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c426t-d7715c616f5387e81dfdb307fc5a43d0a4fa1a3c79861e16151dec7bad39b0f93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>631/337/176/1988</topic><topic>631/67/1536/1665/3016</topic><topic>631/67/2322</topic><topic>Aged</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer</topic><topic>Cancer Research</topic><topic>Case-Control Studies</topic><topic>DCC gene</topic><topic>DCC Receptor - genetics</topic><topic>DNA Methylation</topic><topic>Drug Resistance</topic><topic>Early Detection of Cancer - methods</topic><topic>Epidemiology</topic><topic>Female</topic><topic>Genes, DCC - genetics</topic><topic>Humans</topic><topic>Hypopharyngeal Neoplasms - diagnosis</topic><topic>Hypopharyngeal Neoplasms - genetics</topic><topic>Invasiveness</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Molecular Medicine</topic><topic>Oncology</topic><topic>Pharynx</topic><topic>Promoter Regions, Genetic</topic><topic>Receptor, Endothelin B - genetics</topic><topic>Risk groups</topic><topic>ROC Curve</topic><topic>Saliva</topic><topic>Saliva - chemistry</topic><topic>Throat cancer</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hirai, Ryosuke</creatorcontrib><creatorcontrib>Kinugasa, Hideaki</creatorcontrib><creatorcontrib>Yamamoto, Shumpei</creatorcontrib><creatorcontrib>Ako, Soichiro</creatorcontrib><creatorcontrib>Tsutsumi, Koichiro</creatorcontrib><creatorcontrib>Abe, Makoto</creatorcontrib><creatorcontrib>Miyahara, Koji</creatorcontrib><creatorcontrib>Nakagawa, Masahiro</creatorcontrib><creatorcontrib>Otsuka, Motoyuki</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>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</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>Hirai, Ryosuke</au><au>Kinugasa, Hideaki</au><au>Yamamoto, Shumpei</au><au>Ako, Soichiro</au><au>Tsutsumi, Koichiro</au><au>Abe, Makoto</au><au>Miyahara, Koji</au><au>Nakagawa, Masahiro</au><au>Otsuka, Motoyuki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Methylation analysis of DCC gene in saliva samples is an efficient method for non-invasive detection of superficial hypopharyngeal cancer</atitle><jtitle>British journal of cancer</jtitle><stitle>Br J Cancer</stitle><addtitle>Br J Cancer</addtitle><date>2024-06-01</date><risdate>2024</risdate><volume>130</volume><issue>10</issue><spage>1725</spage><epage>1731</epage><pages>1725-1731</pages><issn>0007-0920</issn><issn>1532-1827</issn><eissn>1532-1827</eissn><abstract>Background
Advances in upper gastrointestinal endoscopic technology have enabled early detection and treatment of hypopharyngeal cancer. However, in-depth pharyngeal observations require sedation and are invasive. It is important to establish a minimally invasive and simple evaluation method to identify high-risk patients.
Methods
Eighty-seven patients with superficial hypopharyngeal cancer and 51 healthy controls were recruited. We assessed the methylation status of
DCC
,
PTGDR1
,
EDNRB
, and
ECAD
, in tissue and saliva samples and verified the diagnostic accuracy by methylation analyses of their promoter regions using quantitative methylation-specific PCR.
Results
Significant differences between cancer and their surrounding non-cancerous tissues were observed in the methylation values of
DCC
(
p
= 0.003),
EDNRB
(
p
= 0.001), and
ECAD
(
p
= 0.043). Using receiver operating characteristic analyses of the methylation values in saliva samples,
DCC
showed the highest area under the curve values for the detection of superficial hypopharyngeal cancer (0.917, 95% confidence interval = 0.864–0.970), compared with those for
EDNRB
(0.680) and
ECAD
(0.639). When the cutoff for the methylation values of
DCC
was set at ≥0.163, the sensitivity to detect hypopharyngeal cancer was 82.8% and the specificity was 90.2%.
Conclusions
DCC
methylation in saliva samples could be a non-invasive and efficient tool for early detection of hypopharyngeal cancer in high-risk patients.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>38538728</pmid><doi>10.1038/s41416-024-02654-2</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0003-4887-1609</orcidid><orcidid>https://orcid.org/0000-0002-3602-9695</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0007-0920 |
| ispartof | British journal of cancer, 2024-06, Vol.130 (10), p.1725-1731 |
| issn | 0007-0920 1532-1827 1532-1827 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11091138 |
| source | MEDLINE; Springer Online Journals Complete |
| subjects | 631/337/176/1988 631/67/1536/1665/3016 631/67/2322 Aged Biomarkers, Tumor - genetics Biomedical and Life Sciences Biomedicine Cancer Cancer Research Case-Control Studies DCC gene DCC Receptor - genetics DNA Methylation Drug Resistance Early Detection of Cancer - methods Epidemiology Female Genes, DCC - genetics Humans Hypopharyngeal Neoplasms - diagnosis Hypopharyngeal Neoplasms - genetics Invasiveness Male Middle Aged Molecular Medicine Oncology Pharynx Promoter Regions, Genetic Receptor, Endothelin B - genetics Risk groups ROC Curve Saliva Saliva - chemistry Throat cancer |
| title | Methylation analysis of DCC gene in saliva samples is an efficient method for non-invasive detection of superficial hypopharyngeal cancer |
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