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Epigenetic markers for noninvasive early detection of nasopharyngeal carcinoma by methylation‐sensitive high resolution melting
Nasopharyngeal carcinoma (NPC) is a human malignancy that is closely associated with Epstein‐Barr Virus (EBV). Early diagnosis of NPC will greatly improve the overall survival. However, current EBV DNA marker detection still lacks the predictive value to perform well in high‐risk populations for ear...
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| Published in: | International journal of cancer 2015-02, Vol.136 (4), p.E127-E135 |
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| container_title | International journal of cancer |
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| creator | Yang, Xuesong Dai, Wei Kwong, Dora Lai‐wan Szeto, Carol Y.Y. Wong, Elibe Hiu‐wun Ng, Wai Tong Lee, Anne W.M. Ngan, Roger K.C. Yau, Chun Chung Tung, Stewart Y. Lung, Maria Li |
| description | Nasopharyngeal carcinoma (NPC) is a human malignancy that is closely associated with Epstein‐Barr Virus (EBV). Early diagnosis of NPC will greatly improve the overall survival. However, current EBV DNA marker detection still lacks the predictive value to perform well in high‐risk populations for early detection of NPC. Since aberrant promoter hypermethylation of tumor suppressor genes (TSGs) is widely considered to be an important epigenetic change in early carcinogenesis, this study identified a panel of methylation markers for early detection of NPC and also assessed the clinical usefulness of these markers with noninvasive plasma specimens instead of biopsies. MS‐HRM assays were carried out to assess the methylation status of a selected panel of four TSGs (RASSF1A, WIF1, DAPK1 and RARβ2) in biopsies, NP brushings and cell‐free plasma from NPC patients. High‐risk and cancer‐free groups were used as controls. DNA methylation panel showed higher sensitivity and specificity than EBV DNA marker in cell‐free plasma from NPC patients at early Stages (I and II) and in addition to the EBV DNA marker, MS‐HRM test for plasma and NP brushing DNA methylation significantly increased the detection rate at all NPC stages as well as local recurrence, using this selected four‐gene panel (p < 0.05). MS‐HRM assay on a selected gene panel has great potential to become a noninvasive and complementary test for NPC early and recurrent detection in combination with the EBV DNA test to increase the sensitivity for NPC detection at an early stage.
What's new?
Tests for Epstein‐Barr virus (EBV) DNA may help screen high‐risk populations for nasopharyngeal carcinoma (NPC), but these tests are not very sensitive. In this study, the authors developed a panel of biomarkers that instead tests for altered methylation of tumor‐suppressor genes. They found that, when plasma and swabs from early‐stage NPC patients were analyzed with the methylation panel, it detected the cancer with higher sensitivity and specificity than tests for EBV DNA. Combining the two tests may enhance noninvasive screening for NPC, thus enabling more timely and effective treatments. |
| doi_str_mv | 10.1002/ijc.29192 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1654692856</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3520962841</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4872-bd0aa11e32da93fdafdb865111c7ceb408131652c7a091a6b1dc54d662dbbeff3</originalsourceid><addsrcrecordid>eNp10bFO3DAcx3GrKipX6NAXqCx1aYeA_07iJCM6UaBC6lLmyLH_ufPVsQ87ocoGb9Bn5EnwcZShUqcM_vgrKz9CPgI7Acb4qdmoE95Aw9-QBbCmyhiH8i1ZpDOWVZCLQ_I-xg1jACUr3pFDXkIjmCgX5OF8a1bocDSKDjL8whBp7wN13hl3J6O5Q4oy2JlqHFGNxjvqe-pk9Nu1DLNbobRUyaCM84Ok3UwHHNezlTv6eP8nootm3GXWZrWmAaO303NmQDsatzomB720ET-8fI_Izbfzn8vL7PrHxdXy7DpTRV3xrNNMSgDMuZZN3mvZ664WJQCoSmFXsBpyECVXlWQNSNGBVmWhheC667Dv8yPyZd_dBn87YRzbwUSF1kqHfoptulyIhtelSPTzP3Tjp-DS65LKCyFqJnhSX_dKBR9jwL7dBpP-4dwCa3e7tGmX9nmXZD-9FKduQP0q_w6RwOke_DYW5_-X2qvvy33yCYuOm5g</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1634668062</pqid></control><display><type>article</type><title>Epigenetic markers for noninvasive early detection of nasopharyngeal carcinoma by methylation‐sensitive high resolution melting</title><source>Wiley Online Library</source><creator>Yang, Xuesong ; Dai, Wei ; Kwong, Dora Lai‐wan ; Szeto, Carol Y.Y. ; Wong, Elibe Hiu‐wun ; Ng, Wai Tong ; Lee, Anne W.M. ; Ngan, Roger K.C. ; Yau, Chun Chung ; Tung, Stewart Y. ; Lung, Maria Li</creator><creatorcontrib>Yang, Xuesong ; Dai, Wei ; Kwong, Dora Lai‐wan ; Szeto, Carol Y.Y. ; Wong, Elibe Hiu‐wun ; Ng, Wai Tong ; Lee, Anne W.M. ; Ngan, Roger K.C. ; Yau, Chun Chung ; Tung, Stewart Y. ; Lung, Maria Li</creatorcontrib><description>Nasopharyngeal carcinoma (NPC) is a human malignancy that is closely associated with Epstein‐Barr Virus (EBV). Early diagnosis of NPC will greatly improve the overall survival. However, current EBV DNA marker detection still lacks the predictive value to perform well in high‐risk populations for early detection of NPC. Since aberrant promoter hypermethylation of tumor suppressor genes (TSGs) is widely considered to be an important epigenetic change in early carcinogenesis, this study identified a panel of methylation markers for early detection of NPC and also assessed the clinical usefulness of these markers with noninvasive plasma specimens instead of biopsies. MS‐HRM assays were carried out to assess the methylation status of a selected panel of four TSGs (RASSF1A, WIF1, DAPK1 and RARβ2) in biopsies, NP brushings and cell‐free plasma from NPC patients. High‐risk and cancer‐free groups were used as controls. DNA methylation panel showed higher sensitivity and specificity than EBV DNA marker in cell‐free plasma from NPC patients at early Stages (I and II) and in addition to the EBV DNA marker, MS‐HRM test for plasma and NP brushing DNA methylation significantly increased the detection rate at all NPC stages as well as local recurrence, using this selected four‐gene panel (p < 0.05). MS‐HRM assay on a selected gene panel has great potential to become a noninvasive and complementary test for NPC early and recurrent detection in combination with the EBV DNA test to increase the sensitivity for NPC detection at an early stage.
What's new?
Tests for Epstein‐Barr virus (EBV) DNA may help screen high‐risk populations for nasopharyngeal carcinoma (NPC), but these tests are not very sensitive. In this study, the authors developed a panel of biomarkers that instead tests for altered methylation of tumor‐suppressor genes. They found that, when plasma and swabs from early‐stage NPC patients were analyzed with the methylation panel, it detected the cancer with higher sensitivity and specificity than tests for EBV DNA. Combining the two tests may enhance noninvasive screening for NPC, thus enabling more timely and effective treatments.</description><identifier>ISSN: 0020-7136</identifier><identifier>EISSN: 1097-0215</identifier><identifier>DOI: 10.1002/ijc.29192</identifier><identifier>PMID: 25196065</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Adult ; Aged ; biomarker ; Biomarkers, Tumor - genetics ; Biopsy ; Cancer ; Carcinoma - blood ; Carcinoma - diagnosis ; Carcinoma - genetics ; Case-Control Studies ; Cell Line, Tumor ; Deoxyribonucleic acid ; DNA ; DNA Methylation ; Early Detection of Cancer ; early diagnosis ; Epigenesis, Genetic ; Epigenetics ; Epstein-Barr virus ; Female ; Genes ; Humans ; Male ; Medical research ; Middle Aged ; MS‐HRM ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms - blood ; Nasopharyngeal Neoplasms - diagnosis ; Nasopharyngeal Neoplasms - genetics ; Neoplasm Recurrence, Local - diagnosis ; Neoplasm Recurrence, Local - genetics ; NPC ; Promoter Regions, Genetic ; ROC Curve ; Transition Temperature</subject><ispartof>International journal of cancer, 2015-02, Vol.136 (4), p.E127-E135</ispartof><rights>2014 UICC</rights><rights>2014 UICC.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4872-bd0aa11e32da93fdafdb865111c7ceb408131652c7a091a6b1dc54d662dbbeff3</citedby><cites>FETCH-LOGICAL-c4872-bd0aa11e32da93fdafdb865111c7ceb408131652c7a091a6b1dc54d662dbbeff3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fijc.29192$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fijc.29192$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,786,790,27957,27958,50923,51032</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25196065$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yang, Xuesong</creatorcontrib><creatorcontrib>Dai, Wei</creatorcontrib><creatorcontrib>Kwong, Dora Lai‐wan</creatorcontrib><creatorcontrib>Szeto, Carol Y.Y.</creatorcontrib><creatorcontrib>Wong, Elibe Hiu‐wun</creatorcontrib><creatorcontrib>Ng, Wai Tong</creatorcontrib><creatorcontrib>Lee, Anne W.M.</creatorcontrib><creatorcontrib>Ngan, Roger K.C.</creatorcontrib><creatorcontrib>Yau, Chun Chung</creatorcontrib><creatorcontrib>Tung, Stewart Y.</creatorcontrib><creatorcontrib>Lung, Maria Li</creatorcontrib><title>Epigenetic markers for noninvasive early detection of nasopharyngeal carcinoma by methylation‐sensitive high resolution melting</title><title>International journal of cancer</title><addtitle>Int J Cancer</addtitle><description>Nasopharyngeal carcinoma (NPC) is a human malignancy that is closely associated with Epstein‐Barr Virus (EBV). Early diagnosis of NPC will greatly improve the overall survival. However, current EBV DNA marker detection still lacks the predictive value to perform well in high‐risk populations for early detection of NPC. Since aberrant promoter hypermethylation of tumor suppressor genes (TSGs) is widely considered to be an important epigenetic change in early carcinogenesis, this study identified a panel of methylation markers for early detection of NPC and also assessed the clinical usefulness of these markers with noninvasive plasma specimens instead of biopsies. MS‐HRM assays were carried out to assess the methylation status of a selected panel of four TSGs (RASSF1A, WIF1, DAPK1 and RARβ2) in biopsies, NP brushings and cell‐free plasma from NPC patients. High‐risk and cancer‐free groups were used as controls. DNA methylation panel showed higher sensitivity and specificity than EBV DNA marker in cell‐free plasma from NPC patients at early Stages (I and II) and in addition to the EBV DNA marker, MS‐HRM test for plasma and NP brushing DNA methylation significantly increased the detection rate at all NPC stages as well as local recurrence, using this selected four‐gene panel (p < 0.05). MS‐HRM assay on a selected gene panel has great potential to become a noninvasive and complementary test for NPC early and recurrent detection in combination with the EBV DNA test to increase the sensitivity for NPC detection at an early stage.
What's new?
Tests for Epstein‐Barr virus (EBV) DNA may help screen high‐risk populations for nasopharyngeal carcinoma (NPC), but these tests are not very sensitive. In this study, the authors developed a panel of biomarkers that instead tests for altered methylation of tumor‐suppressor genes. They found that, when plasma and swabs from early‐stage NPC patients were analyzed with the methylation panel, it detected the cancer with higher sensitivity and specificity than tests for EBV DNA. Combining the two tests may enhance noninvasive screening for NPC, thus enabling more timely and effective treatments.</description><subject>Adult</subject><subject>Aged</subject><subject>biomarker</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biopsy</subject><subject>Cancer</subject><subject>Carcinoma - blood</subject><subject>Carcinoma - diagnosis</subject><subject>Carcinoma - genetics</subject><subject>Case-Control Studies</subject><subject>Cell Line, Tumor</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA Methylation</subject><subject>Early Detection of Cancer</subject><subject>early diagnosis</subject><subject>Epigenesis, Genetic</subject><subject>Epigenetics</subject><subject>Epstein-Barr virus</subject><subject>Female</subject><subject>Genes</subject><subject>Humans</subject><subject>Male</subject><subject>Medical research</subject><subject>Middle Aged</subject><subject>MS‐HRM</subject><subject>Nasopharyngeal Carcinoma</subject><subject>Nasopharyngeal Neoplasms - blood</subject><subject>Nasopharyngeal Neoplasms - diagnosis</subject><subject>Nasopharyngeal Neoplasms - genetics</subject><subject>Neoplasm Recurrence, Local - diagnosis</subject><subject>Neoplasm Recurrence, Local - genetics</subject><subject>NPC</subject><subject>Promoter Regions, Genetic</subject><subject>ROC Curve</subject><subject>Transition Temperature</subject><issn>0020-7136</issn><issn>1097-0215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNp10bFO3DAcx3GrKipX6NAXqCx1aYeA_07iJCM6UaBC6lLmyLH_ufPVsQ87ocoGb9Bn5EnwcZShUqcM_vgrKz9CPgI7Acb4qdmoE95Aw9-QBbCmyhiH8i1ZpDOWVZCLQ_I-xg1jACUr3pFDXkIjmCgX5OF8a1bocDSKDjL8whBp7wN13hl3J6O5Q4oy2JlqHFGNxjvqe-pk9Nu1DLNbobRUyaCM84Ok3UwHHNezlTv6eP8nootm3GXWZrWmAaO303NmQDsatzomB720ET-8fI_Izbfzn8vL7PrHxdXy7DpTRV3xrNNMSgDMuZZN3mvZ664WJQCoSmFXsBpyECVXlWQNSNGBVmWhheC667Dv8yPyZd_dBn87YRzbwUSF1kqHfoptulyIhtelSPTzP3Tjp-DS65LKCyFqJnhSX_dKBR9jwL7dBpP-4dwCa3e7tGmX9nmXZD-9FKduQP0q_w6RwOke_DYW5_-X2qvvy33yCYuOm5g</recordid><startdate>20150215</startdate><enddate>20150215</enddate><creator>Yang, Xuesong</creator><creator>Dai, Wei</creator><creator>Kwong, Dora Lai‐wan</creator><creator>Szeto, Carol Y.Y.</creator><creator>Wong, Elibe Hiu‐wun</creator><creator>Ng, Wai Tong</creator><creator>Lee, Anne W.M.</creator><creator>Ngan, Roger K.C.</creator><creator>Yau, Chun Chung</creator><creator>Tung, Stewart Y.</creator><creator>Lung, Maria Li</creator><general>Wiley Subscription Services, Inc</general><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>7T5</scope><scope>7TO</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>7TM</scope></search><sort><creationdate>20150215</creationdate><title>Epigenetic markers for noninvasive early detection of nasopharyngeal carcinoma by methylation‐sensitive high resolution melting</title><author>Yang, Xuesong ; Dai, Wei ; Kwong, Dora Lai‐wan ; Szeto, Carol Y.Y. ; Wong, Elibe Hiu‐wun ; Ng, Wai Tong ; Lee, Anne W.M. ; Ngan, Roger K.C. ; Yau, Chun Chung ; Tung, Stewart Y. ; Lung, Maria Li</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4872-bd0aa11e32da93fdafdb865111c7ceb408131652c7a091a6b1dc54d662dbbeff3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult</topic><topic>Aged</topic><topic>biomarker</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biopsy</topic><topic>Cancer</topic><topic>Carcinoma - blood</topic><topic>Carcinoma - diagnosis</topic><topic>Carcinoma - genetics</topic><topic>Case-Control Studies</topic><topic>Cell Line, Tumor</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA Methylation</topic><topic>Early Detection of Cancer</topic><topic>early diagnosis</topic><topic>Epigenesis, Genetic</topic><topic>Epigenetics</topic><topic>Epstein-Barr virus</topic><topic>Female</topic><topic>Genes</topic><topic>Humans</topic><topic>Male</topic><topic>Medical research</topic><topic>Middle Aged</topic><topic>MS‐HRM</topic><topic>Nasopharyngeal Carcinoma</topic><topic>Nasopharyngeal Neoplasms - blood</topic><topic>Nasopharyngeal Neoplasms - diagnosis</topic><topic>Nasopharyngeal Neoplasms - genetics</topic><topic>Neoplasm Recurrence, Local - diagnosis</topic><topic>Neoplasm Recurrence, Local - genetics</topic><topic>NPC</topic><topic>Promoter Regions, Genetic</topic><topic>ROC Curve</topic><topic>Transition Temperature</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yang, Xuesong</creatorcontrib><creatorcontrib>Dai, Wei</creatorcontrib><creatorcontrib>Kwong, Dora Lai‐wan</creatorcontrib><creatorcontrib>Szeto, Carol Y.Y.</creatorcontrib><creatorcontrib>Wong, Elibe Hiu‐wun</creatorcontrib><creatorcontrib>Ng, Wai Tong</creatorcontrib><creatorcontrib>Lee, Anne W.M.</creatorcontrib><creatorcontrib>Ngan, Roger K.C.</creatorcontrib><creatorcontrib>Yau, Chun Chung</creatorcontrib><creatorcontrib>Tung, Stewart Y.</creatorcontrib><creatorcontrib>Lung, Maria Li</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</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>Nucleic Acids Abstracts</collection><jtitle>International journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yang, Xuesong</au><au>Dai, Wei</au><au>Kwong, Dora Lai‐wan</au><au>Szeto, Carol Y.Y.</au><au>Wong, Elibe Hiu‐wun</au><au>Ng, Wai Tong</au><au>Lee, Anne W.M.</au><au>Ngan, Roger K.C.</au><au>Yau, Chun Chung</au><au>Tung, Stewart Y.</au><au>Lung, Maria Li</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Epigenetic markers for noninvasive early detection of nasopharyngeal carcinoma by methylation‐sensitive high resolution melting</atitle><jtitle>International journal of cancer</jtitle><addtitle>Int J Cancer</addtitle><date>2015-02-15</date><risdate>2015</risdate><volume>136</volume><issue>4</issue><spage>E127</spage><epage>E135</epage><pages>E127-E135</pages><issn>0020-7136</issn><eissn>1097-0215</eissn><notes>Conflicts of Interest</notes><notes>No potential conflicts of interest were disclosed.</notes><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>Nasopharyngeal carcinoma (NPC) is a human malignancy that is closely associated with Epstein‐Barr Virus (EBV). Early diagnosis of NPC will greatly improve the overall survival. However, current EBV DNA marker detection still lacks the predictive value to perform well in high‐risk populations for early detection of NPC. Since aberrant promoter hypermethylation of tumor suppressor genes (TSGs) is widely considered to be an important epigenetic change in early carcinogenesis, this study identified a panel of methylation markers for early detection of NPC and also assessed the clinical usefulness of these markers with noninvasive plasma specimens instead of biopsies. MS‐HRM assays were carried out to assess the methylation status of a selected panel of four TSGs (RASSF1A, WIF1, DAPK1 and RARβ2) in biopsies, NP brushings and cell‐free plasma from NPC patients. High‐risk and cancer‐free groups were used as controls. DNA methylation panel showed higher sensitivity and specificity than EBV DNA marker in cell‐free plasma from NPC patients at early Stages (I and II) and in addition to the EBV DNA marker, MS‐HRM test for plasma and NP brushing DNA methylation significantly increased the detection rate at all NPC stages as well as local recurrence, using this selected four‐gene panel (p < 0.05). MS‐HRM assay on a selected gene panel has great potential to become a noninvasive and complementary test for NPC early and recurrent detection in combination with the EBV DNA test to increase the sensitivity for NPC detection at an early stage.
What's new?
Tests for Epstein‐Barr virus (EBV) DNA may help screen high‐risk populations for nasopharyngeal carcinoma (NPC), but these tests are not very sensitive. In this study, the authors developed a panel of biomarkers that instead tests for altered methylation of tumor‐suppressor genes. They found that, when plasma and swabs from early‐stage NPC patients were analyzed with the methylation panel, it detected the cancer with higher sensitivity and specificity than tests for EBV DNA. Combining the two tests may enhance noninvasive screening for NPC, thus enabling more timely and effective treatments.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>25196065</pmid><doi>10.1002/ijc.29192</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | International journal of cancer, 2015-02, Vol.136 (4), p.E127-E135 |
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| subjects | Adult Aged biomarker Biomarkers, Tumor - genetics Biopsy Cancer Carcinoma - blood Carcinoma - diagnosis Carcinoma - genetics Case-Control Studies Cell Line, Tumor Deoxyribonucleic acid DNA DNA Methylation Early Detection of Cancer early diagnosis Epigenesis, Genetic Epigenetics Epstein-Barr virus Female Genes Humans Male Medical research Middle Aged MS‐HRM Nasopharyngeal Carcinoma Nasopharyngeal Neoplasms - blood Nasopharyngeal Neoplasms - diagnosis Nasopharyngeal Neoplasms - genetics Neoplasm Recurrence, Local - diagnosis Neoplasm Recurrence, Local - genetics NPC Promoter Regions, Genetic ROC Curve Transition Temperature |
| title | Epigenetic markers for noninvasive early detection of nasopharyngeal carcinoma by methylation‐sensitive high resolution melting |
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