Downregulation of the neonatal Fc receptor expression in non-small cell lung cancer tissue is associated with a poor prognosis.
Identifieur interne : 001B23 ( PubMed/Corpus ); précédent : 001B22; suivant : 001B24Downregulation of the neonatal Fc receptor expression in non-small cell lung cancer tissue is associated with a poor prognosis.
Auteurs : Emilie Dalloneau ; Nadine Baroukh ; Konstantinos Mavridis ; Agnès Maillet ; Fabien Gueugnon ; Yves Courty ; Agnès Petit ; Thomas Kryza ; Maguy Del Rio ; Serge Guyetant ; Diana Carolina Cadena Castaneda ; Christine Dhommée ; Christophe Arnoult ; Andreas Scorilas ; Valérie Gouilleux-Gruart ; Nathalie Heuzé-Vourc'HSource :
- Oncotarget [ 1949-2553 ] ; 2016.
Abstract
Lung cancer is the leading cause of cancer-related death worldwide. Although the recommended tumor, node and metastasis (TNM) classification and stage determination are important to select therapeutic options for patients with non-small cell lung carcinoma (NSCLC), additional molecular markers are required to indicate the prognosis, in particular within a specific stage, and help with the management of patients.Because neonatal Fc receptor (FcRn) has recently been involved in colon cancer immunosurveillance, we measured its expression in non-cancerous and NSCLC lung tissues and evaluated its prognostic value in overall survival for patient with NSCLC. FcRn expression was determined at both mRNA and protein levels on cancerous and adjacent non-cancerous tissues from 80 NSCLC patients. In NSCLC, FcRn was mainly found in resident and tumor infiltrating immune cells. The corresponding mRNA and protein were significantly less abundant in lung tumor than non-cancerous tissue. Moreover, analysis of our cohort and datasets from the public data bases show that FCGRT mRNA down-regulation is a robust and independent, unfavorable predictive factor of NSCLC patient survival. We conclude that FCGRT mRNA expression may be a useful additional marker for immunoscoring, reflecting tumor immune system, and help in the decision-making process for NSCLC patients.
DOI: 10.18632/oncotarget.10074
PubMed: 27384673
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Downregulation of the neonatal Fc receptor expression in non-small cell lung cancer tissue is associated with a poor prognosis.</title><author><name sortKey="Dalloneau, Emilie" sort="Dalloneau, Emilie" uniqKey="Dalloneau E" first="Emilie" last="Dalloneau">Emilie Dalloneau</name><affiliation><nlm:affiliation>Université François Rabelais, UMR 1100, Tours, France.</nlm:affiliation></affiliation></author><author><name sortKey="Baroukh, Nadine" sort="Baroukh, Nadine" uniqKey="Baroukh N" first="Nadine" last="Baroukh">Nadine Baroukh</name><affiliation><nlm:affiliation>Université François Rabelais de Tours, CNRS, GICC UMR 7292, Tours, France.</nlm:affiliation></affiliation></author><author><name sortKey="Mavridis, Konstantinos" sort="Mavridis, Konstantinos" uniqKey="Mavridis K" first="Konstantinos" last="Mavridis">Konstantinos Mavridis</name><affiliation><nlm:affiliation>Department of Biochemistry and Molecular Biology, University of Athens, Panepistimiopolis, Athens, Greece.</nlm:affiliation></affiliation></author><author><name sortKey="Maillet, Agnes" sort="Maillet, Agnes" uniqKey="Maillet A" first="Agnès" last="Maillet">Agnès Maillet</name><affiliation><nlm:affiliation>Université François Rabelais, UMR 1100, Tours, France.</nlm:affiliation></affiliation></author><author><name sortKey="Gueugnon, Fabien" sort="Gueugnon, Fabien" uniqKey="Gueugnon F" first="Fabien" last="Gueugnon">Fabien Gueugnon</name><affiliation><nlm:affiliation>Université François Rabelais, UMR 1100, Tours, France.</nlm:affiliation></affiliation></author><author><name sortKey="Courty, Yves" sort="Courty, Yves" uniqKey="Courty Y" first="Yves" last="Courty">Yves Courty</name><affiliation><nlm:affiliation>Université François Rabelais, UMR 1100, Tours, France.</nlm:affiliation></affiliation></author><author><name sortKey="Petit, Agnes" sort="Petit, Agnes" uniqKey="Petit A" first="Agnès" last="Petit">Agnès Petit</name><affiliation><nlm:affiliation>Université François Rabelais, UMR 1100, Tours, France.</nlm:affiliation></affiliation></author><author><name sortKey="Kryza, Thomas" sort="Kryza, Thomas" uniqKey="Kryza T" first="Thomas" last="Kryza">Thomas Kryza</name><affiliation><nlm:affiliation>Institute of Health and Biomedical Innovation, Translational Research Institute, Queensland University of Technology, Brisbane, Queensland, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Del Rio, Maguy" sort="Del Rio, Maguy" uniqKey="Del Rio M" first="Maguy" last="Del Rio">Maguy Del Rio</name><affiliation><nlm:affiliation>Institut de Recherche en Cancérologie de Montpellier (IRCM), INSERM U1194, Montpellier, France.</nlm:affiliation></affiliation></author><author><name sortKey="Guyetant, Serge" sort="Guyetant, Serge" uniqKey="Guyetant S" first="Serge" last="Guyetant">Serge Guyetant</name><affiliation><nlm:affiliation>Université François Rabelais, UMR 1100, Tours, France.</nlm:affiliation></affiliation></author><author><name sortKey="Cadena Castaneda, Diana Carolina" sort="Cadena Castaneda, Diana Carolina" uniqKey="Cadena Castaneda D" first="Diana Carolina" last="Cadena Castaneda">Diana Carolina Cadena Castaneda</name><affiliation><nlm:affiliation>Université François Rabelais de Tours, CNRS, GICC UMR 7292, Tours, France.</nlm:affiliation></affiliation></author><author><name sortKey="Dhommee, Christine" sort="Dhommee, Christine" uniqKey="Dhommee C" first="Christine" last="Dhommée">Christine Dhommée</name><affiliation><nlm:affiliation>Université François Rabelais de Tours, CNRS, GICC UMR 7292, Tours, France.</nlm:affiliation></affiliation></author><author><name sortKey="Arnoult, Christophe" sort="Arnoult, Christophe" uniqKey="Arnoult C" first="Christophe" last="Arnoult">Christophe Arnoult</name><affiliation><nlm:affiliation>Université François Rabelais de Tours, CNRS, GICC UMR 7292, Tours, France.</nlm:affiliation></affiliation></author><author><name sortKey="Scorilas, Andreas" sort="Scorilas, Andreas" uniqKey="Scorilas A" first="Andreas" last="Scorilas">Andreas Scorilas</name><affiliation><nlm:affiliation>Department of Biochemistry and Molecular Biology, University of Athens, Panepistimiopolis, Athens, Greece.</nlm:affiliation></affiliation></author><author><name sortKey="Gouilleux Gruart, Valerie" sort="Gouilleux Gruart, Valerie" uniqKey="Gouilleux Gruart V" first="Valérie" last="Gouilleux-Gruart">Valérie Gouilleux-Gruart</name><affiliation><nlm:affiliation>Université François Rabelais de Tours, CNRS, GICC UMR 7292, Tours, France.</nlm:affiliation></affiliation></author><author><name sortKey="Heuze Vourc H, Nathalie" sort="Heuze Vourc H, Nathalie" uniqKey="Heuze Vourc H N" first="Nathalie" last="Heuzé-Vourc'H">Nathalie Heuzé-Vourc'H</name><affiliation><nlm:affiliation>Université François Rabelais, UMR 1100, Tours, France.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:27384673</idno><idno type="pmid">27384673</idno><idno type="doi">10.18632/oncotarget.10074</idno><idno type="wicri:Area/PubMed/Corpus">001B23</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001B23</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Downregulation of the neonatal Fc receptor expression in non-small cell lung cancer tissue is associated with a poor prognosis.</title><author><name sortKey="Dalloneau, Emilie" sort="Dalloneau, Emilie" uniqKey="Dalloneau E" first="Emilie" last="Dalloneau">Emilie Dalloneau</name><affiliation><nlm:affiliation>Université François Rabelais, UMR 1100, Tours, France.</nlm:affiliation></affiliation></author><author><name sortKey="Baroukh, Nadine" sort="Baroukh, Nadine" uniqKey="Baroukh N" first="Nadine" last="Baroukh">Nadine Baroukh</name><affiliation><nlm:affiliation>Université François Rabelais de Tours, CNRS, GICC UMR 7292, Tours, France.</nlm:affiliation></affiliation></author><author><name sortKey="Mavridis, Konstantinos" sort="Mavridis, Konstantinos" uniqKey="Mavridis K" first="Konstantinos" last="Mavridis">Konstantinos Mavridis</name><affiliation><nlm:affiliation>Department of Biochemistry and Molecular Biology, University of Athens, Panepistimiopolis, Athens, Greece.</nlm:affiliation></affiliation></author><author><name sortKey="Maillet, Agnes" sort="Maillet, Agnes" uniqKey="Maillet A" first="Agnès" last="Maillet">Agnès Maillet</name><affiliation><nlm:affiliation>Université François Rabelais, UMR 1100, Tours, France.</nlm:affiliation></affiliation></author><author><name sortKey="Gueugnon, Fabien" sort="Gueugnon, Fabien" uniqKey="Gueugnon F" first="Fabien" last="Gueugnon">Fabien Gueugnon</name><affiliation><nlm:affiliation>Université François Rabelais, UMR 1100, Tours, France.</nlm:affiliation></affiliation></author><author><name sortKey="Courty, Yves" sort="Courty, Yves" uniqKey="Courty Y" first="Yves" last="Courty">Yves Courty</name><affiliation><nlm:affiliation>Université François Rabelais, UMR 1100, Tours, France.</nlm:affiliation></affiliation></author><author><name sortKey="Petit, Agnes" sort="Petit, Agnes" uniqKey="Petit A" first="Agnès" last="Petit">Agnès Petit</name><affiliation><nlm:affiliation>Université François Rabelais, UMR 1100, Tours, France.</nlm:affiliation></affiliation></author><author><name sortKey="Kryza, Thomas" sort="Kryza, Thomas" uniqKey="Kryza T" first="Thomas" last="Kryza">Thomas Kryza</name><affiliation><nlm:affiliation>Institute of Health and Biomedical Innovation, Translational Research Institute, Queensland University of Technology, Brisbane, Queensland, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Del Rio, Maguy" sort="Del Rio, Maguy" uniqKey="Del Rio M" first="Maguy" last="Del Rio">Maguy Del Rio</name><affiliation><nlm:affiliation>Institut de Recherche en Cancérologie de Montpellier (IRCM), INSERM U1194, Montpellier, France.</nlm:affiliation></affiliation></author><author><name sortKey="Guyetant, Serge" sort="Guyetant, Serge" uniqKey="Guyetant S" first="Serge" last="Guyetant">Serge Guyetant</name><affiliation><nlm:affiliation>Université François Rabelais, UMR 1100, Tours, France.</nlm:affiliation></affiliation></author><author><name sortKey="Cadena Castaneda, Diana Carolina" sort="Cadena Castaneda, Diana Carolina" uniqKey="Cadena Castaneda D" first="Diana Carolina" last="Cadena Castaneda">Diana Carolina Cadena Castaneda</name><affiliation><nlm:affiliation>Université François Rabelais de Tours, CNRS, GICC UMR 7292, Tours, France.</nlm:affiliation></affiliation></author><author><name sortKey="Dhommee, Christine" sort="Dhommee, Christine" uniqKey="Dhommee C" first="Christine" last="Dhommée">Christine Dhommée</name><affiliation><nlm:affiliation>Université François Rabelais de Tours, CNRS, GICC UMR 7292, Tours, France.</nlm:affiliation></affiliation></author><author><name sortKey="Arnoult, Christophe" sort="Arnoult, Christophe" uniqKey="Arnoult C" first="Christophe" last="Arnoult">Christophe Arnoult</name><affiliation><nlm:affiliation>Université François Rabelais de Tours, CNRS, GICC UMR 7292, Tours, France.</nlm:affiliation></affiliation></author><author><name sortKey="Scorilas, Andreas" sort="Scorilas, Andreas" uniqKey="Scorilas A" first="Andreas" last="Scorilas">Andreas Scorilas</name><affiliation><nlm:affiliation>Department of Biochemistry and Molecular Biology, University of Athens, Panepistimiopolis, Athens, Greece.</nlm:affiliation></affiliation></author><author><name sortKey="Gouilleux Gruart, Valerie" sort="Gouilleux Gruart, Valerie" uniqKey="Gouilleux Gruart V" first="Valérie" last="Gouilleux-Gruart">Valérie Gouilleux-Gruart</name><affiliation><nlm:affiliation>Université François Rabelais de Tours, CNRS, GICC UMR 7292, Tours, France.</nlm:affiliation></affiliation></author><author><name sortKey="Heuze Vourc H, Nathalie" sort="Heuze Vourc H, Nathalie" uniqKey="Heuze Vourc H N" first="Nathalie" last="Heuzé-Vourc'H">Nathalie Heuzé-Vourc'H</name><affiliation><nlm:affiliation>Université François Rabelais, UMR 1100, Tours, France.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Oncotarget</title><idno type="eISSN">1949-2553</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Lung cancer is the leading cause of cancer-related death worldwide. Although the recommended tumor, node and metastasis (TNM) classification and stage determination are important to select therapeutic options for patients with non-small cell lung carcinoma (NSCLC), additional molecular markers are required to indicate the prognosis, in particular within a specific stage, and help with the management of patients.Because neonatal Fc receptor (FcRn) has recently been involved in colon cancer immunosurveillance, we measured its expression in non-cancerous and NSCLC lung tissues and evaluated its prognostic value in overall survival for patient with NSCLC. FcRn expression was determined at both mRNA and protein levels on cancerous and adjacent non-cancerous tissues from 80 NSCLC patients. In NSCLC, FcRn was mainly found in resident and tumor infiltrating immune cells. The corresponding mRNA and protein were significantly less abundant in lung tumor than non-cancerous tissue. Moreover, analysis of our cohort and datasets from the public data bases show that FCGRT mRNA down-regulation is a robust and independent, unfavorable predictive factor of NSCLC patient survival. We conclude that FCGRT mRNA expression may be a useful additional marker for immunoscoring, reflecting tumor immune system, and help in the decision-making process for NSCLC patients.</div></front></TEI><pubmed><MedlineCitation Status="In-Process" Owner="NLM"><PMID Version="1">27384673</PMID><DateCreated><Year>2016</Year><Month>07</Month><Day>07</Day></DateCreated><DateRevised><Year>2017</Year><Month>03</Month><Day>23</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1949-2553</ISSN><JournalIssue CitedMedium="Internet"><Volume>7</Volume><Issue>34</Issue><PubDate><Year>2016</Year><Month>08</Month><Day>23</Day></PubDate></JournalIssue><Title>Oncotarget</Title><ISOAbbreviation>Oncotarget</ISOAbbreviation></Journal><ArticleTitle>Downregulation of the neonatal Fc receptor expression in non-small cell lung cancer tissue is associated with a poor prognosis.</ArticleTitle><Pagination><MedlinePgn>54415-54429</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.18632/oncotarget.10074</ELocationID><Abstract><AbstractText>Lung cancer is the leading cause of cancer-related death worldwide. Although the recommended tumor, node and metastasis (TNM) classification and stage determination are important to select therapeutic options for patients with non-small cell lung carcinoma (NSCLC), additional molecular markers are required to indicate the prognosis, in particular within a specific stage, and help with the management of patients.Because neonatal Fc receptor (FcRn) has recently been involved in colon cancer immunosurveillance, we measured its expression in non-cancerous and NSCLC lung tissues and evaluated its prognostic value in overall survival for patient with NSCLC. FcRn expression was determined at both mRNA and protein levels on cancerous and adjacent non-cancerous tissues from 80 NSCLC patients. In NSCLC, FcRn was mainly found in resident and tumor infiltrating immune cells. The corresponding mRNA and protein were significantly less abundant in lung tumor than non-cancerous tissue. Moreover, analysis of our cohort and datasets from the public data bases show that FCGRT mRNA down-regulation is a robust and independent, unfavorable predictive factor of NSCLC patient survival. We conclude that FCGRT mRNA expression may be a useful additional marker for immunoscoring, reflecting tumor immune system, and help in the decision-making process for NSCLC patients.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Dalloneau</LastName><ForeName>Emilie</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Université François Rabelais, UMR 1100, Tours, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>INSERM, Centre d'Etude des Pathologies Respiratoires, UMR 1100, Tours, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Baroukh</LastName><ForeName>Nadine</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Université François Rabelais de Tours, CNRS, GICC UMR 7292, Tours, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mavridis</LastName><ForeName>Konstantinos</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Biology, University of Athens, Panepistimiopolis, Athens, Greece.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Maillet</LastName><ForeName>Agnès</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Université François Rabelais, UMR 1100, Tours, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>INSERM, Centre d'Etude des Pathologies Respiratoires, UMR 1100, Tours, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gueugnon</LastName><ForeName>Fabien</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Université François Rabelais, UMR 1100, Tours, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>INSERM, Centre d'Etude des Pathologies Respiratoires, UMR 1100, Tours, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Courty</LastName><ForeName>Yves</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Université François Rabelais, UMR 1100, Tours, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>INSERM, Centre d'Etude des Pathologies Respiratoires, UMR 1100, Tours, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Petit</LastName><ForeName>Agnès</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Université François Rabelais, UMR 1100, Tours, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>INSERM, Centre d'Etude des Pathologies Respiratoires, UMR 1100, Tours, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kryza</LastName><ForeName>Thomas</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Institute of Health and Biomedical Innovation, Translational Research Institute, Queensland University of Technology, Brisbane, Queensland, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Del Rio</LastName><ForeName>Maguy</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Institut de Recherche en Cancérologie de Montpellier (IRCM), INSERM U1194, Montpellier, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Guyetant</LastName><ForeName>Serge</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Université François Rabelais, UMR 1100, Tours, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>INSERM, Centre d'Etude des Pathologies Respiratoires, UMR 1100, Tours, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cadena Castaneda</LastName><ForeName>Diana Carolina</ForeName><Initials>DC</Initials><AffiliationInfo><Affiliation>Université François Rabelais de Tours, CNRS, GICC UMR 7292, Tours, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dhommée</LastName><ForeName>Christine</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Université François Rabelais de Tours, CNRS, GICC UMR 7292, Tours, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Arnoult</LastName><ForeName>Christophe</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Université François Rabelais de Tours, CNRS, GICC UMR 7292, Tours, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Scorilas</LastName><ForeName>Andreas</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Biology, University of Athens, Panepistimiopolis, Athens, Greece.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gouilleux-Gruart</LastName><ForeName>Valérie</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Université François Rabelais de Tours, CNRS, GICC UMR 7292, Tours, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>CHRU de TOURS, Laboratoire d'Immunologie, Tours, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Heuzé-Vourc'h</LastName><ForeName>Nathalie</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Université François Rabelais, UMR 1100, Tours, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>INSERM, Centre d'Etude des Pathologies Respiratoires, UMR 1100, Tours, France.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Oncotarget</MedlineTA><NlmUniqueID>101532965</NlmUniqueID><ISSNLinking>1949-2553</ISSNLinking></MedlineJournalInfo><CommentsCorrectionsList><CommentsCorrections RefType="Cites"><RefSource>Proc Natl Acad Sci U S A. 2011 Jun 14;108(24):9927-32</RefSource><PMID Version="1">21628593</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Clin Oncol. 2010 Oct 10;28(29):4417-24</RefSource><PMID 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PubStatus="medline"><Year>2016</Year><Month>7</Month><Day>8</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2016</Year><Month>7</Month><Day>8</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">27384673</ArticleId><ArticleId IdType="pii">10074</ArticleId><ArticleId IdType="doi">10.18632/oncotarget.10074</ArticleId><ArticleId IdType="pmc">PMC5342352</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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