Multiple genetic and epigenetic biomarkers for lung cancer detection in cytologically negative sputum and a nested case-control study for risk assessment
The purpose of this study was to define a biomarker panel for detection of cancer cells in cytologically negative sputum and to evaluate the panel for assessment of lung cancer risk. We examined 19 genetic and epigenetic markers using a sensitive fluorescence-based method in cytologically negative s...
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| Veröffentlicht in: | The Journal of pathology 2007-12, Vol.213 (4), p.412-419 |
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| creator | Hsu, H.S Chen, T.P Wen, C.K Hung, C.H Chen, C.Y Chen, J.T Wang, Y.C |
| description | The purpose of this study was to define a biomarker panel for detection of cancer cells in cytologically negative sputum and to evaluate the panel for assessment of lung cancer risk. We examined 19 genetic and epigenetic markers using a sensitive fluorescence-based method in cytologically negative sputum and in lung tumour tissues from 82 lung cancer patients. We also used these markers to test the sputum of 37 cancer-free individuals who were matched by age, sex, and smoking habit. Based on the concordance of biomarkers in lung tumours and corresponding sputum, and the low prevalence in cancer-free individuals, we selected seven markers for a nested case-control study: microsatellite instability of D9S942; loss of heterozygosity of D9S286, D9S942, GATA49D12, and D13S170; and methylation of p16INK4a and RARβ. Based on the assumption that a lung cancer cell has alterations in two or more of the seven biomarkers, we compared the pattern of biomarker alteration in lung tumours and corresponding sputum. Our comparison yielded a sensitivity of 82%, specificity of 75%, and concordance of 79%. Three cancer-free individuals were considered to have an elevated risk based on the criterion that their sputum showed alteration in two of the seven biomarkers. One individual was indeed diagnosed as having lung cancer 18 months after sputum collection. In the nested case-control study, six biomarkers showed significantly increased odds ratios ranging from 3.14 to 11.24. Our study defines a biomarker panel for detection of cancer cells in cytologically negative sputum and verifies its use for risk assessment of lung cancer. In combination with conventional diagnostic tools, this multiple genetic and epigenetic panel should improve the detection or risk assessment of lung cancer. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
| doi_str_mv | 10.1002/path.2246 |
| format | Article |
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We examined 19 genetic and epigenetic markers using a sensitive fluorescence-based method in cytologically negative sputum and in lung tumour tissues from 82 lung cancer patients. We also used these markers to test the sputum of 37 cancer-free individuals who were matched by age, sex, and smoking habit. Based on the concordance of biomarkers in lung tumours and corresponding sputum, and the low prevalence in cancer-free individuals, we selected seven markers for a nested case-control study: microsatellite instability of D9S942; loss of heterozygosity of D9S286, D9S942, GATA49D12, and D13S170; and methylation of p16INK4a and RARβ. Based on the assumption that a lung cancer cell has alterations in two or more of the seven biomarkers, we compared the pattern of biomarker alteration in lung tumours and corresponding sputum. Our comparison yielded a sensitivity of 82%, specificity of 75%, and concordance of 79%. Three cancer-free individuals were considered to have an elevated risk based on the criterion that their sputum showed alteration in two of the seven biomarkers. One individual was indeed diagnosed as having lung cancer 18 months after sputum collection. In the nested case-control study, six biomarkers showed significantly increased odds ratios ranging from 3.14 to 11.24. Our study defines a biomarker panel for detection of cancer cells in cytologically negative sputum and verifies its use for risk assessment of lung cancer. In combination with conventional diagnostic tools, this multiple genetic and epigenetic panel should improve the detection or risk assessment of lung cancer. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.</description><identifier>ISSN: 0022-3417</identifier><identifier>EISSN: 1096-9896</identifier><identifier>DOI: 10.1002/path.2246</identifier><identifier>PMID: 17973238</identifier><identifier>CODEN: JPTLAS</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Acid Anhydride Hydrolases - genetics ; Base Sequence ; Biological and medical sciences ; Biomarkers, Tumor - genetics ; Carcinoma, Non-Small-Cell Lung - diagnosis ; Carcinoma, Non-Small-Cell Lung - genetics ; Carcinoma, Non-Small-Cell Lung - pathology ; Case-Control Studies ; case-control study ; DNA Methylation ; Epigenesis, Genetic ; Female ; Genes, p16 ; Genetic Markers ; Humans ; Investigative techniques, diagnostic techniques (general aspects) ; LOH ; Loss of Heterozygosity ; Lung Neoplasms - diagnosis ; Lung Neoplasms - genetics ; Lung Neoplasms - pathology ; Male ; Medical sciences ; Microsatellite Instability ; Molecular Sequence Data ; MSI ; MSP ; Neoplasm Proteins - genetics ; Neoplasm Staging ; NSCLC ; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques ; Pneumology ; Promoter Regions, Genetic - genetics ; Receptors, Retinoic Acid - genetics ; Risk Assessment - methods ; Sensitivity and Specificity ; sputum ; Sputum - cytology ; Tumors of the respiratory system and mediastinum</subject><ispartof>The Journal of pathology, 2007-12, Vol.213 (4), p.412-419</ispartof><rights>Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.</rights><rights>2008 INIST-CNRS</rights><rights>(c) 2007 Pathological Society of Great Britain and Ireland</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4156-f080a21d44a7f0ad1c05835a33247fe9e08296b0cd523379f8ea1acbf583cfe73</citedby><cites>FETCH-LOGICAL-c4156-f080a21d44a7f0ad1c05835a33247fe9e08296b0cd523379f8ea1acbf583cfe73</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%2Fpath.2246$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpath.2246$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=19438623$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17973238$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hsu, H.S</creatorcontrib><creatorcontrib>Chen, T.P</creatorcontrib><creatorcontrib>Wen, C.K</creatorcontrib><creatorcontrib>Hung, C.H</creatorcontrib><creatorcontrib>Chen, C.Y</creatorcontrib><creatorcontrib>Chen, J.T</creatorcontrib><creatorcontrib>Wang, Y.C</creatorcontrib><title>Multiple genetic and epigenetic biomarkers for lung cancer detection in cytologically negative sputum and a nested case-control study for risk assessment</title><title>The Journal of pathology</title><addtitle>J. Pathol</addtitle><description>The purpose of this study was to define a biomarker panel for detection of cancer cells in cytologically negative sputum and to evaluate the panel for assessment of lung cancer risk. We examined 19 genetic and epigenetic markers using a sensitive fluorescence-based method in cytologically negative sputum and in lung tumour tissues from 82 lung cancer patients. We also used these markers to test the sputum of 37 cancer-free individuals who were matched by age, sex, and smoking habit. Based on the concordance of biomarkers in lung tumours and corresponding sputum, and the low prevalence in cancer-free individuals, we selected seven markers for a nested case-control study: microsatellite instability of D9S942; loss of heterozygosity of D9S286, D9S942, GATA49D12, and D13S170; and methylation of p16INK4a and RARβ. Based on the assumption that a lung cancer cell has alterations in two or more of the seven biomarkers, we compared the pattern of biomarker alteration in lung tumours and corresponding sputum. Our comparison yielded a sensitivity of 82%, specificity of 75%, and concordance of 79%. Three cancer-free individuals were considered to have an elevated risk based on the criterion that their sputum showed alteration in two of the seven biomarkers. One individual was indeed diagnosed as having lung cancer 18 months after sputum collection. In the nested case-control study, six biomarkers showed significantly increased odds ratios ranging from 3.14 to 11.24. Our study defines a biomarker panel for detection of cancer cells in cytologically negative sputum and verifies its use for risk assessment of lung cancer. In combination with conventional diagnostic tools, this multiple genetic and epigenetic panel should improve the detection or risk assessment of lung cancer. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.</description><subject>Acid Anhydride Hydrolases - genetics</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Carcinoma, Non-Small-Cell Lung - diagnosis</subject><subject>Carcinoma, Non-Small-Cell Lung - genetics</subject><subject>Carcinoma, Non-Small-Cell Lung - pathology</subject><subject>Case-Control Studies</subject><subject>case-control study</subject><subject>DNA Methylation</subject><subject>Epigenesis, Genetic</subject><subject>Female</subject><subject>Genes, p16</subject><subject>Genetic Markers</subject><subject>Humans</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>LOH</subject><subject>Loss of Heterozygosity</subject><subject>Lung Neoplasms - diagnosis</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - pathology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Microsatellite Instability</subject><subject>Molecular Sequence Data</subject><subject>MSI</subject><subject>MSP</subject><subject>Neoplasm Proteins - genetics</subject><subject>Neoplasm Staging</subject><subject>NSCLC</subject><subject>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</subject><subject>Pneumology</subject><subject>Promoter Regions, Genetic - genetics</subject><subject>Receptors, Retinoic Acid - genetics</subject><subject>Risk Assessment - methods</subject><subject>Sensitivity and Specificity</subject><subject>sputum</subject><subject>Sputum - cytology</subject><subject>Tumors of the respiratory system and mediastinum</subject><issn>0022-3417</issn><issn>1096-9896</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc1uEzEUhS0EomlgwQuAN1RiMa1_ZsbjZVVoglR-BK1YWo7nOpg648H2AHkU3hanCXTFyrLvd8-9PgehZ5ScUkLY2ajz11PG6vYBmlEi20p2sn2IZqXGKl5TcYSOU_pGCJGyaR6jIyqk4Ix3M_T73eSzGz3gNQyQncF66DGM7u915cJGx1uICdsQsZ-GNTZ6MBBxDxlMdmHAbsBmm4MPa2e091s8wFpn9wNwGqc8be5EdXlNGfrSnqAyYcgxeJzy1G_vpKNLt1inBCltYMhP0COrfYKnh3OObi7fXF8sq6sPi7cX51eVqWnTVpZ0RDPa17UWluieGtJ0vNGcs1pYkEA6JtsVMX3DOBfSdqCpNitbKGNB8Dk62euOMXyfyoZq45IB7_UAYUqq7RpCOZMFfLUHTQwpRbBqjK54s1WUqF0OapeD2uVQ2OcH0Wm1gf6ePBhfgJcHQKdimY3FUpfuOVnzri0Lz9HZnvvpPGz_P1F9PL9eHkZX-w5XzP71r6NkqFrBRaO-vF-o15fLuv0kmFoU_sWetzoovS4pqJvPrHyZFOeE5JT_AeFEu3I</recordid><startdate>200712</startdate><enddate>200712</enddate><creator>Hsu, H.S</creator><creator>Chen, T.P</creator><creator>Wen, C.K</creator><creator>Hung, C.H</creator><creator>Chen, C.Y</creator><creator>Chen, J.T</creator><creator>Wang, Y.C</creator><general>John Wiley & Sons, Ltd</general><general>Wiley</general><scope>FBQ</scope><scope>BSCLL</scope><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>7X8</scope></search><sort><creationdate>200712</creationdate><title>Multiple genetic and epigenetic biomarkers for lung cancer detection in cytologically negative sputum and a nested case-control study for risk assessment</title><author>Hsu, H.S ; Chen, T.P ; Wen, C.K ; Hung, C.H ; Chen, C.Y ; Chen, J.T ; Wang, Y.C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4156-f080a21d44a7f0ad1c05835a33247fe9e08296b0cd523379f8ea1acbf583cfe73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Acid Anhydride Hydrolases - genetics</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Carcinoma, Non-Small-Cell Lung - diagnosis</topic><topic>Carcinoma, Non-Small-Cell Lung - genetics</topic><topic>Carcinoma, Non-Small-Cell Lung - pathology</topic><topic>Case-Control Studies</topic><topic>case-control study</topic><topic>DNA Methylation</topic><topic>Epigenesis, Genetic</topic><topic>Female</topic><topic>Genes, p16</topic><topic>Genetic Markers</topic><topic>Humans</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>LOH</topic><topic>Loss of Heterozygosity</topic><topic>Lung Neoplasms - diagnosis</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - pathology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Microsatellite Instability</topic><topic>Molecular Sequence Data</topic><topic>MSI</topic><topic>MSP</topic><topic>Neoplasm Proteins - genetics</topic><topic>Neoplasm Staging</topic><topic>NSCLC</topic><topic>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</topic><topic>Pneumology</topic><topic>Promoter Regions, Genetic - genetics</topic><topic>Receptors, Retinoic Acid - genetics</topic><topic>Risk Assessment - methods</topic><topic>Sensitivity and Specificity</topic><topic>sputum</topic><topic>Sputum - cytology</topic><topic>Tumors of the respiratory system and mediastinum</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hsu, H.S</creatorcontrib><creatorcontrib>Chen, T.P</creatorcontrib><creatorcontrib>Wen, C.K</creatorcontrib><creatorcontrib>Hung, C.H</creatorcontrib><creatorcontrib>Chen, C.Y</creatorcontrib><creatorcontrib>Chen, J.T</creatorcontrib><creatorcontrib>Wang, Y.C</creatorcontrib><collection>AGRIS</collection><collection>Istex</collection><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>MEDLINE - Academic</collection><jtitle>The Journal of pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hsu, H.S</au><au>Chen, T.P</au><au>Wen, C.K</au><au>Hung, C.H</au><au>Chen, C.Y</au><au>Chen, J.T</au><au>Wang, Y.C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Multiple genetic and epigenetic biomarkers for lung cancer detection in cytologically negative sputum and a nested case-control study for risk assessment</atitle><jtitle>The Journal of pathology</jtitle><addtitle>J. Pathol</addtitle><date>2007-12</date><risdate>2007</risdate><volume>213</volume><issue>4</issue><spage>412</spage><epage>419</epage><pages>412-419</pages><issn>0022-3417</issn><eissn>1096-9896</eissn><coden>JPTLAS</coden><abstract>The purpose of this study was to define a biomarker panel for detection of cancer cells in cytologically negative sputum and to evaluate the panel for assessment of lung cancer risk. We examined 19 genetic and epigenetic markers using a sensitive fluorescence-based method in cytologically negative sputum and in lung tumour tissues from 82 lung cancer patients. We also used these markers to test the sputum of 37 cancer-free individuals who were matched by age, sex, and smoking habit. Based on the concordance of biomarkers in lung tumours and corresponding sputum, and the low prevalence in cancer-free individuals, we selected seven markers for a nested case-control study: microsatellite instability of D9S942; loss of heterozygosity of D9S286, D9S942, GATA49D12, and D13S170; and methylation of p16INK4a and RARβ. Based on the assumption that a lung cancer cell has alterations in two or more of the seven biomarkers, we compared the pattern of biomarker alteration in lung tumours and corresponding sputum. Our comparison yielded a sensitivity of 82%, specificity of 75%, and concordance of 79%. Three cancer-free individuals were considered to have an elevated risk based on the criterion that their sputum showed alteration in two of the seven biomarkers. One individual was indeed diagnosed as having lung cancer 18 months after sputum collection. In the nested case-control study, six biomarkers showed significantly increased odds ratios ranging from 3.14 to 11.24. Our study defines a biomarker panel for detection of cancer cells in cytologically negative sputum and verifies its use for risk assessment of lung cancer. In combination with conventional diagnostic tools, this multiple genetic and epigenetic panel should improve the detection or risk assessment of lung cancer. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>17973238</pmid><doi>10.1002/path.2246</doi><tpages>8</tpages></addata></record> |
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| subjects | Acid Anhydride Hydrolases - genetics Base Sequence Biological and medical sciences Biomarkers, Tumor - genetics Carcinoma, Non-Small-Cell Lung - diagnosis Carcinoma, Non-Small-Cell Lung - genetics Carcinoma, Non-Small-Cell Lung - pathology Case-Control Studies case-control study DNA Methylation Epigenesis, Genetic Female Genes, p16 Genetic Markers Humans Investigative techniques, diagnostic techniques (general aspects) LOH Loss of Heterozygosity Lung Neoplasms - diagnosis Lung Neoplasms - genetics Lung Neoplasms - pathology Male Medical sciences Microsatellite Instability Molecular Sequence Data MSI MSP Neoplasm Proteins - genetics Neoplasm Staging NSCLC Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques Pneumology Promoter Regions, Genetic - genetics Receptors, Retinoic Acid - genetics Risk Assessment - methods Sensitivity and Specificity sputum Sputum - cytology Tumors of the respiratory system and mediastinum |
| title | Multiple genetic and epigenetic biomarkers for lung cancer detection in cytologically negative sputum and a nested case-control study for risk assessment |
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