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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Identification of two clinical hepatocellular carcinoma patient phenotypes from results of standard screening parameters</title><author><name sortKey="Carr, Brian I" sort="Carr, Brian I" uniqKey="Carr B" first="Brian I." last="Carr">Brian I. Carr</name><affiliation><nlm:aff id="A1">Department of Liver Tumor Biology IRCCS de Bellis, National Institute for Digestive Diseases, Castellana Grotte , BA, Italy</nlm:aff></affiliation></author><author><name sortKey="Pancoska, Petr" sort="Pancoska, Petr" uniqKey="Pancoska P" first="Petr" last="Pancoska">Petr Pancoska</name><affiliation><nlm:aff id="A2">Center for Craniofacial and Dental Genetics, University of Pittsburgh, Pittsburgh, PA, USA</nlm:aff></affiliation></author><author><name sortKey="Giannini, Edoardo G" sort="Giannini, Edoardo G" uniqKey="Giannini E" first="Edoardo G." last="Giannini">Edoardo G. Giannini</name><affiliation><nlm:aff id="A3">Department of Internal Medicine, Gastroenterology Unit, University of Genoa</nlm:aff></affiliation></author><author><name sortKey="Farinati, Fabio" sort="Farinati, Fabio" uniqKey="Farinati F" first="Fabio" last="Farinati">Fabio Farinati</name><affiliation><nlm:aff id="A4">Department of Surgical Science and Gastroenterology, Gastroenterology Unit, University of Padua</nlm:aff></affiliation></author><author><name sortKey="Ciccarese, Francesca" sort="Ciccarese, Francesca" uniqKey="Ciccarese F" first="Francesca" last="Ciccarese">Francesca Ciccarese</name><affiliation><nlm:aff id="A5">Division of Surgery, Policlinico San Marco, Zingonia</nlm:aff></affiliation></author><author><name sortKey="Rapaccini, Gian Ludovico" sort="Rapaccini, Gian Ludovico" uniqKey="Rapaccini G" first="Gian Ludovico" last="Rapaccini">Gian Ludovico Rapaccini</name><affiliation><nlm:aff id="A6">Internal Medicine and Gastroenterology Unit, Catholic University of Rome, Rome</nlm:aff></affiliation></author><author><name sortKey="Marco, Maria Di" sort="Marco, Maria Di" uniqKey="Marco M" first="Maria Di" last="Marco">Maria Di Marco</name><affiliation><nlm:aff id="A7">Division of Medicine, Azienda Ospedaliera Bolognini, Seriate</nlm:aff></affiliation></author><author><name sortKey="Benvegnu, Luisa" sort="Benvegnu, Luisa" uniqKey="Benvegnu L" first="Luisa" last="Benvegnù">Luisa Benvegnù</name><affiliation><nlm:aff id="A8">Departiment of Clinical and Experimental Medicine, Medical Unit, University of Padua</nlm:aff></affiliation></author><author><name sortKey="Zoli, Marco" sort="Zoli, Marco" uniqKey="Zoli M" first="Marco" last="Zoli">Marco Zoli</name><affiliation><nlm:aff id="A9">Department of Medical and Surgical Science, Internal Medicine Unit, Alma Mater Studiorum – University of Bologna</nlm:aff></affiliation></author><author><name sortKey="Borzio, Franco" sort="Borzio, Franco" uniqKey="Borzio F" first="Franco" last="Borzio">Franco Borzio</name><affiliation><nlm:aff id="A10">Department of Medicine, Internal Medicine and Hepatology Unit, Ospedale Fatebenefratelli, Milan</nlm:aff></affiliation></author><author><name sortKey="Caturelli, Eugenio" sort="Caturelli, Eugenio" uniqKey="Caturelli E" first="Eugenio" last="Caturelli">Eugenio Caturelli</name><affiliation><nlm:aff id="A11">Gastroenterology Unit, Ospedale Belcolle, Viterbo</nlm:aff></affiliation></author><author><name sortKey="Chiaramonte, Maria" sort="Chiaramonte, Maria" uniqKey="Chiaramonte M" first="Maria" last="Chiaramonte">Maria Chiaramonte</name><affiliation><nlm:aff id="A12">Gastroenterology Unit, Ospedale Sacro Cuore Don Calabria, Negrar</nlm:aff></affiliation></author><author><name sortKey="Trevisani, Franco" sort="Trevisani, Franco" uniqKey="Trevisani F" first="Franco" last="Trevisani">Franco Trevisani</name><affiliation><nlm:aff id="A13">Department of Medical Surgical Sciences, Medical Semiotics Unit, Alma Mater Studiorum – University of Bologna, Italy.</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25023357</idno><idno type="pmc">4109657</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4109657</idno><idno type="RBID">PMC:4109657</idno><idno type="doi">10.1053/j.seminoncol.2014.04.002</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">000F42</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000F42</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Identification of two clinical hepatocellular carcinoma patient phenotypes from results of standard screening parameters</title><author><name sortKey="Carr, Brian I" sort="Carr, Brian I" uniqKey="Carr B" first="Brian I." last="Carr">Brian I. Carr</name><affiliation><nlm:aff id="A1">Department of Liver Tumor Biology IRCCS de Bellis, National Institute for Digestive Diseases, Castellana Grotte , BA, Italy</nlm:aff></affiliation></author><author><name sortKey="Pancoska, Petr" sort="Pancoska, Petr" uniqKey="Pancoska P" first="Petr" last="Pancoska">Petr Pancoska</name><affiliation><nlm:aff id="A2">Center for Craniofacial and Dental Genetics, University of Pittsburgh, Pittsburgh, PA, USA</nlm:aff></affiliation></author><author><name sortKey="Giannini, Edoardo G" sort="Giannini, Edoardo G" uniqKey="Giannini E" first="Edoardo G." last="Giannini">Edoardo G. Giannini</name><affiliation><nlm:aff id="A3">Department of Internal Medicine, Gastroenterology Unit, University of Genoa</nlm:aff></affiliation></author><author><name sortKey="Farinati, Fabio" sort="Farinati, Fabio" uniqKey="Farinati F" first="Fabio" last="Farinati">Fabio Farinati</name><affiliation><nlm:aff id="A4">Department of Surgical Science and Gastroenterology, Gastroenterology Unit, University of Padua</nlm:aff></affiliation></author><author><name sortKey="Ciccarese, Francesca" sort="Ciccarese, Francesca" uniqKey="Ciccarese F" first="Francesca" last="Ciccarese">Francesca Ciccarese</name><affiliation><nlm:aff id="A5">Division of Surgery, Policlinico San Marco, Zingonia</nlm:aff></affiliation></author><author><name sortKey="Rapaccini, Gian Ludovico" sort="Rapaccini, Gian Ludovico" uniqKey="Rapaccini G" first="Gian Ludovico" last="Rapaccini">Gian Ludovico Rapaccini</name><affiliation><nlm:aff id="A6">Internal Medicine and Gastroenterology Unit, Catholic University of Rome, Rome</nlm:aff></affiliation></author><author><name sortKey="Marco, Maria Di" sort="Marco, Maria Di" uniqKey="Marco M" first="Maria Di" last="Marco">Maria Di Marco</name><affiliation><nlm:aff id="A7">Division of Medicine, Azienda Ospedaliera Bolognini, Seriate</nlm:aff></affiliation></author><author><name sortKey="Benvegnu, Luisa" sort="Benvegnu, Luisa" uniqKey="Benvegnu L" first="Luisa" last="Benvegnù">Luisa Benvegnù</name><affiliation><nlm:aff id="A8">Departiment of Clinical and Experimental Medicine, Medical Unit, University of Padua</nlm:aff></affiliation></author><author><name sortKey="Zoli, Marco" sort="Zoli, Marco" uniqKey="Zoli M" first="Marco" last="Zoli">Marco Zoli</name><affiliation><nlm:aff id="A9">Department of Medical and Surgical Science, Internal Medicine Unit, Alma Mater Studiorum – University of Bologna</nlm:aff></affiliation></author><author><name sortKey="Borzio, Franco" sort="Borzio, Franco" uniqKey="Borzio F" first="Franco" last="Borzio">Franco Borzio</name><affiliation><nlm:aff id="A10">Department of Medicine, Internal Medicine and Hepatology Unit, Ospedale Fatebenefratelli, Milan</nlm:aff></affiliation></author><author><name sortKey="Caturelli, Eugenio" sort="Caturelli, Eugenio" uniqKey="Caturelli E" first="Eugenio" last="Caturelli">Eugenio Caturelli</name><affiliation><nlm:aff id="A11">Gastroenterology Unit, Ospedale Belcolle, Viterbo</nlm:aff></affiliation></author><author><name sortKey="Chiaramonte, Maria" sort="Chiaramonte, Maria" uniqKey="Chiaramonte M" first="Maria" last="Chiaramonte">Maria Chiaramonte</name><affiliation><nlm:aff id="A12">Gastroenterology Unit, Ospedale Sacro Cuore Don Calabria, Negrar</nlm:aff></affiliation></author><author><name sortKey="Trevisani, Franco" sort="Trevisani, Franco" uniqKey="Trevisani F" first="Franco" last="Trevisani">Franco Trevisani</name><affiliation><nlm:aff id="A13">Department of Medical Surgical Sciences, Medical Semiotics Unit, Alma Mater Studiorum – University of Bologna, Italy.</nlm:aff></affiliation></author></analytic><series><title level="j">Seminars in oncology</title><idno type="ISSN">0093-7754</idno><idno type="eISSN">1532-8708</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="S1"><title>Background</title><p id="P1">Previous work has shown that 2 general processes contribute to hepatocellular cancer (HCC) prognosis. They are: a. liver damage, monitored by indices such as blood bilirubin, prothrombin time and AST; as well as b. tumor biology, monitored by indices such as tumor size, tumor number, presence of PVT and blood AFP levels. These 2 processes may affect one another, with prognostically significant interactions between multiple tumor and host parameters. These interactions form a context that provide personalization of the prognostic meaning of these factors for every patient. Thus, a given level of bilirubin or tumor diameter might have a different significance in different personal contexts. We previously applied Network Phenotyping Strategy (NPS) to characterize interactions between liver function indices of Asian HCC patients and recognized two clinical phenotypes, S and L, differing in tumor size and tumor nodule numbers.</p></sec><sec id="S2"><title>Aims</title><p id="P2">To validate the applicability of the NPS-based HCC S/L classification on an independent European HCC cohort, for which survival information was additionally available.</p></sec><sec id="S3"><title>Methods</title><p id="P3">Four sets of peripheral blood parameters, including AFP-platelets, derived from routine blood parameter levels and tumor indices from the ITA.LI.CA database, were analyzed using NPS, a graph-theory based approach, which compares personal patterns of complete relationships between clinical data values to reference patterns with significant association to disease outcomes.</p></sec><sec id="S4"><title>Results</title><p id="P4">Without reference to the actual tumor sizes, patients were classified by NPS into 2 subgroups with S and L phenotypes. These two phenotypes were recognized using solely the HCC screening test results, consisting of eight common blood parameters, paired by their significant correlations, including an AFP-Platelets relationship. These trends were combined with patient age, gender and self-reported alcoholism into NPS personal patient profiles. We subsequently validated (using actual scan data) that patients in L phenotype group had 1.5x larger mean tumor masses relative to S, <italic>p</italic>=6×10<sup>−16</sup>. Importantly, with the new data, liver test pattern-identified S-phenotype patients had typically 1.7 × longer survival compared to L-phenotype. NPS integrated the liver, tumor and basic demographic factors. Cirrhosis associated thrombocytopenia was typical for smaller S-tumors. In L-tumor phenotype, typical platelet levels increased with the tumor mass. Hepatic inflammation and tumor factors contributed to more aggressive L tumors, with parenchymal destruction and shorter survival.</p></sec><sec id="S5"><title>Summary</title><p id="P5">NPS provides integrative interpretation for HCC behavior, identifying two tumor and survival phenotypes by clinical parameter patterns. The NPS classifier is provided as an Excel tool. The NPS system shows the importance of considering each tumor marker and parameter in the total context of all the other parameters of an individual patient.</p></sec></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">0420432</journal-id><journal-id journal-id-type="pubmed-jr-id">7488</journal-id><journal-id journal-id-type="nlm-ta">Semin Oncol</journal-id><journal-id journal-id-type="iso-abbrev">Semin. Oncol.</journal-id><journal-title-group><journal-title>Seminars in oncology</journal-title></journal-title-group><issn pub-type="ppub">0093-7754</issn><issn pub-type="epub">1532-8708</issn></journal-meta><article-meta><article-id pub-id-type="pmid">25023357</article-id><article-id pub-id-type="pmc">4109657</article-id><article-id pub-id-type="doi">10.1053/j.seminoncol.2014.04.002</article-id><article-id pub-id-type="manuscript">NIHMS589280</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Identification of two clinical hepatocellular carcinoma patient phenotypes from results of standard screening parameters</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Carr</surname><given-names>Brian I.</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Pancoska</surname><given-names>Petr</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Giannini</surname><given-names>Edoardo G.</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Farinati</surname><given-names>Fabio</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Ciccarese</surname><given-names>Francesca</given-names></name><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Rapaccini</surname><given-names>Gian Ludovico</given-names></name><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Marco</surname><given-names>Maria Di</given-names></name><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author"><name><surname>Benvegnù</surname><given-names>Luisa</given-names></name><xref ref-type="aff" rid="A8">8</xref></contrib><contrib contrib-type="author"><name><surname>Zoli</surname><given-names>Marco</given-names></name><xref ref-type="aff" rid="A9">9</xref></contrib><contrib contrib-type="author"><name><surname>Borzio</surname><given-names>Franco</given-names></name><xref ref-type="aff" rid="A10">10</xref></contrib><contrib contrib-type="author"><name><surname>Caturelli</surname><given-names>Eugenio</given-names></name><xref ref-type="aff" rid="A11">11</xref></contrib><contrib contrib-type="author"><name><surname>Chiaramonte</surname><given-names>Maria</given-names></name><xref ref-type="aff" rid="A12">12</xref></contrib><contrib contrib-type="author"><name><surname>Trevisani</surname><given-names>Franco</given-names></name><xref ref-type="aff" rid="A13">13</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><collab>the Italian Liver Cancer (ITA.LI.CA) group</collab></contrib></contrib-group><aff id="A1"><label>1</label>Department of Liver Tumor Biology IRCCS de Bellis, National Institute for Digestive Diseases, Castellana Grotte , BA, Italy</aff><aff id="A2"><label>2</label>Center for Craniofacial and Dental Genetics, University of Pittsburgh, Pittsburgh, PA, USA</aff><aff id="A3"><label>3</label>Department of Internal Medicine, Gastroenterology Unit, University of Genoa</aff><aff id="A4"><label>4</label>Department of Surgical Science and Gastroenterology, Gastroenterology Unit, University of Padua</aff><aff id="A5"><label>5</label>Division of Surgery, Policlinico San Marco, Zingonia</aff><aff id="A6"><label>6</label>Internal Medicine and Gastroenterology Unit, Catholic University of Rome, Rome</aff><aff id="A7"><label>7</label>Division of Medicine, Azienda Ospedaliera Bolognini, Seriate</aff><aff id="A8"><label>8</label>Departiment of Clinical and Experimental Medicine, Medical Unit, University of Padua</aff><aff id="A9"><label>9</label>Department of Medical and Surgical Science, Internal Medicine Unit, Alma Mater Studiorum – University of Bologna</aff><aff id="A10"><label>10</label>Department of Medicine, Internal Medicine and Hepatology Unit, Ospedale Fatebenefratelli, Milan</aff><aff id="A11"><label>11</label>Gastroenterology Unit, Ospedale Belcolle, Viterbo</aff><aff id="A12"><label>12</label>Gastroenterology Unit, Ospedale Sacro Cuore Don Calabria, Negrar</aff><aff id="A13"><label>13</label>Department of Medical Surgical Sciences, Medical Semiotics Unit, Alma Mater Studiorum – University of Bologna, Italy.</aff><author-notes><corresp id="CR1"><bold>Correspondence</bold>: Brian I. Carr MD, FRCP, PhD IRCCS ‘S. de Bellis’, via Turi 27, 70013 Castellana Grotte (BA), Italy Tel. 39 080 4994603; Fax. 39 080 4994313 <email>brianicarr@hotmail.com</email></corresp></author-notes><pub-date pub-type="nihms-submitted"><day>23</day><month>5</month><year>2014</year></pub-date><pub-date pub-type="epub"><day>24</day><month>4</month><year>2014</year></pub-date><pub-date pub-type="ppub"><month>6</month><year>2014</year></pub-date><pub-date pub-type="pmc-release"><day>01</day><month>6</month><year>2015</year></pub-date><volume>41</volume><issue>3</issue><fpage>406</fpage><lpage>414</lpage><pmc-comment>elocation-id from pubmed: 10.1053/j.seminoncol.2014.04.002</pmc-comment>
<permissions><copyright-statement>© 2014 Elsevier Inc. All rights reserved.</copyright-statement><copyright-year>2014</copyright-year></permissions><abstract><sec id="S1"><title>Background</title><p id="P1">Previous work has shown that 2 general processes contribute to hepatocellular cancer (HCC) prognosis. They are: a. liver damage, monitored by indices such as blood bilirubin, prothrombin time and AST; as well as b. tumor biology, monitored by indices such as tumor size, tumor number, presence of PVT and blood AFP levels. These 2 processes may affect one another, with prognostically significant interactions between multiple tumor and host parameters. These interactions form a context that provide personalization of the prognostic meaning of these factors for every patient. Thus, a given level of bilirubin or tumor diameter might have a different significance in different personal contexts. We previously applied Network Phenotyping Strategy (NPS) to characterize interactions between liver function indices of Asian HCC patients and recognized two clinical phenotypes, S and L, differing in tumor size and tumor nodule numbers.</p></sec><sec id="S2"><title>Aims</title><p id="P2">To validate the applicability of the NPS-based HCC S/L classification on an independent European HCC cohort, for which survival information was additionally available.</p></sec><sec id="S3"><title>Methods</title><p id="P3">Four sets of peripheral blood parameters, including AFP-platelets, derived from routine blood parameter levels and tumor indices from the ITA.LI.CA database, were analyzed using NPS, a graph-theory based approach, which compares personal patterns of complete relationships between clinical data values to reference patterns with significant association to disease outcomes.</p></sec><sec id="S4"><title>Results</title><p id="P4">Without reference to the actual tumor sizes, patients were classified by NPS into 2 subgroups with S and L phenotypes. These two phenotypes were recognized using solely the HCC screening test results, consisting of eight common blood parameters, paired by their significant correlations, including an AFP-Platelets relationship. These trends were combined with patient age, gender and self-reported alcoholism into NPS personal patient profiles. We subsequently validated (using actual scan data) that patients in L phenotype group had 1.5x larger mean tumor masses relative to S, <italic>p</italic>=6×10<sup>−16</sup>. Importantly, with the new data, liver test pattern-identified S-phenotype patients had typically 1.7 × longer survival compared to L-phenotype. NPS integrated the liver, tumor and basic demographic factors. Cirrhosis associated thrombocytopenia was typical for smaller S-tumors. In L-tumor phenotype, typical platelet levels increased with the tumor mass. Hepatic inflammation and tumor factors contributed to more aggressive L tumors, with parenchymal destruction and shorter survival.</p></sec><sec id="S5"><title>Summary</title><p id="P5">NPS provides integrative interpretation for HCC behavior, identifying two tumor and survival phenotypes by clinical parameter patterns. The NPS classifier is provided as an Excel tool. The NPS system shows the importance of considering each tumor marker and parameter in the total context of all the other parameters of an individual patient.</p></sec></abstract><kwd-group><kwd>HCC</kwd><kwd>tumor mass</kwd><kwd>survival</kwd><kwd>AFP</kwd><kwd>network phenotyping</kwd><kwd>platelets</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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