Validation of biomarkers that complement CA19.9 in detecting early pancreatic cancer
Identifieur interne : 000906 ( Main/Exploration ); précédent : 000905; suivant : 000907Validation of biomarkers that complement CA19.9 in detecting early pancreatic cancer
Auteurs : Alison Chan [Canada] ; Ioannis Prassas [Canada] ; Apostolos Dimitromanolakis [Canada] ; Randall Brand [États-Unis] ; Stefano Serra [Canada] ; Eleftherios P. Diamandis [Canada] ; Ivan M. Blasutig [Canada]Source :
- Clinical cancer research : an official journal of the American Association for Cancer Research [ 1078-0432 ] ; 2014.
Descripteurs français
- KwdFr :
- Adulte, Adulte d'âge moyen, Antigène CA 19-9 (métabolisme), Antigène CA 19-9 (sang), Antigènes CA-125 (sang), Courbe ROC, Facteurs de risque, Femelle, Humains, Laminine (sang), Marqueurs biologiques tumoraux, Mâle, Reproductibilité des résultats, Stade de la tumeur, Sujet âgé, Tumeurs du pancréas (anatomopathologie), Tumeurs du pancréas (diagnostic), Tumeurs du pancréas (métabolisme), Études cas-témoins.
- MESH :
- anatomopathologie : Tumeurs du pancréas.
- diagnostic : Tumeurs du pancréas.
- métabolisme : Antigène CA 19-9, Tumeurs du pancréas.
- sang : Antigène CA 19-9, Antigènes CA-125, Laminine.
- Adulte, Adulte d'âge moyen, Courbe ROC, Facteurs de risque, Femelle, Humains, Marqueurs biologiques tumoraux, Mâle, Reproductibilité des résultats, Stade de la tumeur, Sujet âgé, Études cas-témoins.
English descriptors
- KwdEn :
- Adult, Aged, Biomarkers, Tumor, CA-125 Antigen (blood), CA-19-9 Antigen (blood), CA-19-9 Antigen (metabolism), Case-Control Studies, Female, Humans, Laminin (blood), Male, Middle Aged, Neoplasm Staging, Pancreatic Neoplasms (diagnosis), Pancreatic Neoplasms (metabolism), Pancreatic Neoplasms (pathology), ROC Curve, Reproducibility of Results, Risk Factors.
- MESH :
- chemical , blood : CA-125 Antigen, CA-19-9 Antigen, Laminin.
- chemical , metabolism : CA-19-9 Antigen.
- chemical : Biomarkers, Tumor.
- diagnosis : Pancreatic Neoplasms.
- metabolism : Pancreatic Neoplasms.
- pathology : Pancreatic Neoplasms.
- Adult, Aged, Case-Control Studies, Female, Humans, Male, Middle Aged, Neoplasm Staging, ROC Curve, Reproducibility of Results, Risk Factors.
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a significant cause of cancer mortality. CA19.9, the only tumor marker available to detect and monitor PDAC, is not sufficiently sensitive and specific to consistently differentiate early cancer from benign disease. In this study we aimed to validate recently discovered serum protein biomarkers for the early detection of PDAC and ultimately develop a biomarker panel that could discriminate PDAC from other benign disease better than the existing marker CA19.9.
We performed a retrospective blinded evaluation of 400 serum samples collected from individuals recruited on a consecutive basis. The sample population consisted of 250 individuals with PDAC at various stages, 130 individuals with benign conditions and 20 healthy individuals. The serum levels of each biomarker were determined by ELISAs or automated immunoassay.
By randomly splitting matched samples into a training (n=186) and validation (n=214) set we were able to develop and validate a biomarker panel consisting of CA19.9, CA125 and LAMC2 that significantly improved the performance of CA19.9 alone. Improved discrimination was observed in the validation set between all PDAC and benign conditions (AUCCA19.9=0.80 versus AUCCA19.9+CA125+LAMC2= 0.87; p<0.005) as well as between early-stage PDAC and benign conditions (AUCCA19.9 = 0.69 versus AUCCA19.9+CA125+LAMC2 = 0.76; p<0.05) and between early-stage PDAC and chronic pancreatitis (AUCCA19.9 = 0.59 versus AUCCA19.9+CA125+LAMC2 = 0.74; p<0.05).
The data demonstrate that a serum protein biomarker panel consisting of CA125, CA19.9 and LAMC2 is able to significantly improve upon the performance of CA19.9 alone in detecting PDAC.
Url:
DOI: 10.1158/1078-0432.CCR-14-0289
PubMed: 25239611
PubMed Central: 4233184
Affiliations:
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xml:lang="fr">Canada</country><wicri:regionArea>Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON</wicri:regionArea><wicri:noRegion>ON</wicri:noRegion></affiliation></author><author><name sortKey="Brand, Randall" sort="Brand, Randall" uniqKey="Brand R" first="Randall" last="Brand">Randall Brand</name><affiliation wicri:level="2"><nlm:aff id="A4">University of Pittsburgh, Division of Gastroenterology, Hepatology & Nutrition, Pittsburgh, PA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>University of Pittsburgh, Division of Gastroenterology, Hepatology & Nutrition, Pittsburgh</wicri:cityArea></affiliation></author><author><name sortKey="Serra, Stefano" sort="Serra, Stefano" uniqKey="Serra S" first="Stefano" last="Serra">Stefano Serra</name><affiliation wicri:level="4"><nlm:aff id="A1">Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="A5">Department of Pathology, University Health Network, Toronto, ON, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Pathology, University Health Network, Toronto, ON</wicri:regionArea><wicri:noRegion>ON</wicri:noRegion></affiliation></author><author><name sortKey="Diamandis, Eleftherios P" sort="Diamandis, Eleftherios P" uniqKey="Diamandis E" first="Eleftherios P." last="Diamandis">Eleftherios P. Diamandis</name><affiliation wicri:level="4"><nlm:aff id="A1">Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON</wicri:regionArea><wicri:noRegion>ON</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">Department of Clinical Biochemistry, University Health Network, Toronto, ON, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Clinical Biochemistry, University Health Network, Toronto, ON</wicri:regionArea><wicri:noRegion>ON</wicri:noRegion></affiliation></author><author><name sortKey="Blasutig, Ivan M" sort="Blasutig, Ivan M" uniqKey="Blasutig I" first="Ivan M." last="Blasutig">Ivan M. Blasutig</name><affiliation wicri:level="4"><nlm:aff id="A1">Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">Department of Clinical Biochemistry, University Health Network, Toronto, ON, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Clinical Biochemistry, University Health Network, Toronto, ON</wicri:regionArea><wicri:noRegion>ON</wicri:noRegion></affiliation></author></analytic><series><title level="j">Clinical cancer research : an official journal of the American Association for Cancer Research</title><idno type="ISSN">1078-0432</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Aged</term><term>Biomarkers, Tumor</term><term>CA-125 Antigen (blood)</term><term>CA-19-9 Antigen (blood)</term><term>CA-19-9 Antigen (metabolism)</term><term>Case-Control Studies</term><term>Female</term><term>Humans</term><term>Laminin (blood)</term><term>Male</term><term>Middle Aged</term><term>Neoplasm Staging</term><term>Pancreatic Neoplasms (diagnosis)</term><term>Pancreatic Neoplasms (metabolism)</term><term>Pancreatic Neoplasms (pathology)</term><term>ROC Curve</term><term>Reproducibility of Results</term><term>Risk Factors</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adulte</term><term>Adulte d'âge moyen</term><term>Antigène CA 19-9 (métabolisme)</term><term>Antigène CA 19-9 (sang)</term><term>Antigènes CA-125 (sang)</term><term>Courbe ROC</term><term>Facteurs de risque</term><term>Femelle</term><term>Humains</term><term>Laminine (sang)</term><term>Marqueurs biologiques tumoraux</term><term>Mâle</term><term>Reproductibilité des résultats</term><term>Stade de la tumeur</term><term>Sujet âgé</term><term>Tumeurs du pancréas (anatomopathologie)</term><term>Tumeurs du pancréas (diagnostic)</term><term>Tumeurs du pancréas (métabolisme)</term><term>Études cas-témoins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>CA-125 Antigen</term><term>CA-19-9 Antigen</term><term>Laminin</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>CA-19-9 Antigen</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Biomarkers, Tumor</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Tumeurs du pancréas</term></keywords><keywords scheme="MESH" qualifier="diagnosis" xml:lang="en"><term>Pancreatic Neoplasms</term></keywords><keywords scheme="MESH" qualifier="diagnostic" xml:lang="fr"><term>Tumeurs du pancréas</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Pancreatic Neoplasms</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Antigène CA 19-9</term><term>Tumeurs du pancréas</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Pancreatic Neoplasms</term></keywords><keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Antigène CA 19-9</term><term>Antigènes CA-125</term><term>Laminine</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Aged</term><term>Case-Control Studies</term><term>Female</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Neoplasm Staging</term><term>ROC Curve</term><term>Reproducibility of Results</term><term>Risk Factors</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adulte</term><term>Adulte d'âge moyen</term><term>Courbe ROC</term><term>Facteurs de risque</term><term>Femelle</term><term>Humains</term><term>Marqueurs biologiques tumoraux</term><term>Mâle</term><term>Reproductibilité des résultats</term><term>Stade de la tumeur</term><term>Sujet âgé</term><term>Études cas-témoins</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="S1"><title>Purpose</title><p id="P2">Pancreatic ductal adenocarcinoma (PDAC) is a significant cause of cancer mortality. CA19.9, the only tumor marker available to detect and monitor PDAC, is not sufficiently sensitive and specific to consistently differentiate early cancer from benign disease. In this study we aimed to validate recently discovered serum protein biomarkers for the early detection of PDAC and ultimately develop a biomarker panel that could discriminate PDAC from other benign disease better than the existing marker CA19.9.</p></sec><sec id="S2"><title>Patients and Methods</title><p id="P3">We performed a retrospective blinded evaluation of 400 serum samples collected from individuals recruited on a consecutive basis. The sample population consisted of 250 individuals with PDAC at various stages, 130 individuals with benign conditions and 20 healthy individuals. The serum levels of each biomarker were determined by ELISAs or automated immunoassay.</p></sec><sec id="S3"><title>Results</title><p id="P4">By randomly splitting matched samples into a training (n=186) and validation (n=214) set we were able to develop and validate a biomarker panel consisting of CA19.9, CA125 and LAMC2 that significantly improved the performance of CA19.9 alone. Improved discrimination was observed in the validation set between all PDAC and benign conditions (AUC<sub>CA19.9</sub>=0.80 versus AUC<sub>CA19.9+CA125+LAMC2</sub>= 0.87; p<0.005) as well as between early-stage PDAC and benign conditions (AUC<sub>CA19.9</sub> = 0.69 versus AUC<sub>CA19.9+CA125+LAMC2</sub> = 0.76; p<0.05) and between early-stage PDAC and chronic pancreatitis (AUC<sub>CA19.9</sub> = 0.59 versus AUC<sub>CA19.9+CA125+LAMC2</sub> = 0.74; p<0.05).</p></sec><sec id="S4"><title>Conclusions</title><p id="P5">The data demonstrate that a serum protein biomarker panel consisting of CA125, CA19.9 and LAMC2 is able to significantly improve upon the performance of CA19.9 alone in detecting PDAC.</p></sec></div></front></TEI><affiliations><list><country><li>Canada</li><li>États-Unis</li></country><region><li>Ontario</li><li>Pennsylvanie</li></region><settlement><li>Toronto</li></settlement><orgName><li>Université de Toronto</li></orgName></list><tree><country name="Canada"><region name="Ontario"><name sortKey="Chan, Alison" sort="Chan, Alison" uniqKey="Chan A" first="Alison" last="Chan">Alison Chan</name></region><name sortKey="Blasutig, Ivan M" sort="Blasutig, Ivan M" uniqKey="Blasutig I" first="Ivan M." last="Blasutig">Ivan M. Blasutig</name><name sortKey="Blasutig, Ivan M" sort="Blasutig, Ivan M" uniqKey="Blasutig I" first="Ivan M." last="Blasutig">Ivan M. Blasutig</name><name sortKey="Chan, Alison" sort="Chan, Alison" uniqKey="Chan A" first="Alison" last="Chan">Alison Chan</name><name sortKey="Diamandis, Eleftherios P" sort="Diamandis, Eleftherios P" uniqKey="Diamandis E" first="Eleftherios P." last="Diamandis">Eleftherios P. Diamandis</name><name sortKey="Diamandis, Eleftherios P" sort="Diamandis, Eleftherios P" uniqKey="Diamandis E" first="Eleftherios P." last="Diamandis">Eleftherios P. Diamandis</name><name sortKey="Diamandis, Eleftherios P" sort="Diamandis, Eleftherios P" uniqKey="Diamandis E" first="Eleftherios P." last="Diamandis">Eleftherios P. Diamandis</name><name sortKey="Dimitromanolakis, Apostolos" sort="Dimitromanolakis, Apostolos" uniqKey="Dimitromanolakis A" first="Apostolos" last="Dimitromanolakis">Apostolos Dimitromanolakis</name><name sortKey="Prassas, Ioannis" sort="Prassas, Ioannis" uniqKey="Prassas I" first="Ioannis" last="Prassas">Ioannis Prassas</name><name sortKey="Prassas, Ioannis" sort="Prassas, Ioannis" uniqKey="Prassas I" first="Ioannis" last="Prassas">Ioannis Prassas</name><name sortKey="Serra, Stefano" sort="Serra, Stefano" uniqKey="Serra S" first="Stefano" last="Serra">Stefano Serra</name><name sortKey="Serra, Stefano" sort="Serra, Stefano" uniqKey="Serra S" first="Stefano" last="Serra">Stefano Serra</name></country><country name="États-Unis"><region name="Pennsylvanie"><name sortKey="Brand, Randall" sort="Brand, Randall" uniqKey="Brand R" first="Randall" last="Brand">Randall Brand</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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