Autophagy-related Proteins as a Prognostic Factor of Patients With Colorectal Cancer
Identifieur interne : 000A27 ( Ncbi/Merge ); précédent : 000A26; suivant : 000A28Autophagy-related Proteins as a Prognostic Factor of Patients With Colorectal Cancer
Auteurs : Evangelos Koustas ; Panagiotis Sarantis ; Stamatios Theoharis ; Angelica A. Saetta ; Ilenia Chatziandreou ; Georgia Kyriakopoulou ; Ioanna Giannopoulou ; Maria Michelli ; Dimitrios Schizas ; Athanasios G. Papavassiliou ; Michalis V. Karamouzis [Grèce]Source :
- American Journal of Clinical Oncology [ 0277-3732 ] ; 2019.
Abstract
Supplemental Digital Content is available in the text.
Url:
DOI: 10.1097/COC.0000000000000592
PubMed: 31517637
PubMed Central: 6766360
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Zhu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Koustas, E" uniqKey="Koustas E">E Koustas</name></author><author><name sortKey="Papavassiliou, Ag" uniqKey="Papavassiliou A">AG Papavassiliou</name></author><author><name sortKey="Karamouzis, Mv" uniqKey="Karamouzis M">MV Karamouzis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xu, Y" uniqKey="Xu Y">Y Xu</name></author><author><name sortKey="Cai, X" uniqKey="Cai X">X Cai</name></author><author><name sortKey="Zong, B" uniqKey="Zong B">B Zong</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Am J Clin Oncol</journal-id><journal-id journal-id-type="iso-abbrev">Am. J. Clin. Oncol</journal-id><journal-id journal-id-type="publisher-id">COC</journal-id><journal-title-group><journal-title>American Journal of Clinical Oncology</journal-title></journal-title-group><issn pub-type="ppub">0277-3732</issn><issn pub-type="epub">1537-453X</issn><publisher><publisher-name>Lippincott Williams & Wilkins</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31517637</article-id><article-id pub-id-type="pmc">6766360</article-id><article-id pub-id-type="doi">10.1097/COC.0000000000000592</article-id><article-id pub-id-type="art-access-id">00006</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Articles: Gastrointestinal</subject></subj-group></article-categories><title-group><article-title>Autophagy-related Proteins as a Prognostic Factor of Patients With Colorectal Cancer</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Koustas</surname><given-names>Evangelos</given-names></name><degrees>MD, PhD</degrees><xref ref-type="aff" rid="aff1">*</xref></contrib><contrib contrib-type="author"><name><surname>Sarantis</surname><given-names>Panagiotis</given-names></name><degrees>MSc</degrees><xref ref-type="aff" rid="aff1">*</xref></contrib><contrib contrib-type="author"><name><surname>Theoharis</surname><given-names>Stamatios</given-names></name><degrees>MD, PhD</degrees><xref ref-type="aff" rid="aff2">†</xref></contrib><contrib contrib-type="author"><name><surname>Saetta</surname><given-names>Angelica A.</given-names></name><degrees>MD, PhD</degrees><xref ref-type="aff" rid="aff2">†</xref></contrib><contrib contrib-type="author"><name><surname>Chatziandreou</surname><given-names>Ilenia</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="aff2">†</xref></contrib><contrib contrib-type="author"><name><surname>Kyriakopoulou</surname><given-names>Georgia</given-names></name><degrees>MSc</degrees><xref ref-type="aff" rid="aff1">*</xref></contrib><contrib contrib-type="author"><name><surname>Giannopoulou</surname><given-names>Ioanna</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="aff2">†</xref></contrib><contrib contrib-type="author"><name><surname>Michelli</surname><given-names>Maria</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="aff2">†</xref></contrib><contrib contrib-type="author"><name><surname>Schizas</surname><given-names>Dimitrios</given-names></name><degrees>MD, PhD</degrees><xref ref-type="aff" rid="aff3">‡</xref></contrib><contrib contrib-type="author"><name><surname>Papavassiliou</surname><given-names>Athanasios G.</given-names></name><degrees>MD, PhD</degrees><xref ref-type="aff" rid="aff1">*</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Karamouzis</surname><given-names>Michalis V.</given-names></name><degrees>MD, PhD</degrees><xref ref-type="aff" rid="aff1">*</xref><xref ref-type="aff" rid="aff4">§</xref></contrib></contrib-group><aff id="aff1"><label>*</label>Molecular Oncology Unit, Department of Biological Chemistry</aff><aff id="aff2"><label>†</label>Department of Pathology</aff><aff id="aff3"><label>‡</label>First Department of Surgery</aff><aff id="aff4"><label>§</label>First Department of Internal Medicine, Laiko Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece</aff><author-notes><corresp>Reprints: Michalis V. Karamouzis, MD, PhD, Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75, M. Asias Street, Athens 11527, Greece. E-mail: <email>mkaramouz@med.uoa.gr</email>.</corresp></author-notes><pub-date pub-type="ppub"><month>10</month><year>2019</year></pub-date><pub-date pub-type="epub"><day>11</day><month>9</month><year>2019</year></pub-date><volume>42</volume><issue>10</issue><fpage>767</fpage><lpage>776</lpage><permissions><copyright-statement>Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc.</copyright-statement><copyright-year>2019</copyright-year><license license-type="open-access"><license-p>This is an open-access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc-nd/4.0/">Creative Commons Attribution-Non Commercial-No Derivatives License 4.0</ext-link> (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc-nd/4.0/">http://creativecommons.org/licenses/by-nc-nd/4.0/</ext-link></license-p></license></permissions><self-uri xlink:type="simple" xlink:href="coc-42-767.pdf"></self-uri><abstract abstract-type="toc"><p>Supplemental Digital Content is available in the text.</p></abstract><abstract><title>Objectives:</title><p>Autophagy plays a dual role in tumorigenesis. In the initial stages, it promotes cell survival and suppresses carcinogenesis, whereas in cancer development, it induces cancer cell survival. In this study, we investigate the role of autophagy as a protective or tumor suppressor mechanism in colorectal cancer (CRC) cell lines and evaluate its role as a potential biomarker in human tumor samples.</p><sec><title>Materials and Methods:</title><p>The data of 68 patients with CRC treated at our Department from January 1 to December 31, 2016 were analyzed. Immunohistochemistry evaluation of p62, LC3B, Beclin-1, and Rab-7 in formalin-fixed paraffin-embedded tissue samples was performed and their expression was correlated with clinicopathologic characteristics, mutation status, and therapeutic approach. The χ<sup>2</sup> was used to test an association among categorical variables. Survival curves were estimated using the Kaplan-Meier method and differences were assessed using the log-rank test. Colo-205, HT29, SW-480, and Caco-2 cell lines were also used so as to test the autophagy markers with oxaliplatin, irinotecan, hydroxychloroquine, and 3-methyladenine.</p></sec><sec><title>Results:</title><p>Overexpression of Beclin-1 is associated with poor survival (<italic>P</italic>=0.001) in patients with CRC treated with chemotherapy, irrespective of the stage and mutational status. Rab-7 is also correlated with progression-free survival (PFS) (<italic>P</italic>=0.088). Oxaliplatin (10 and 20 μΜ) and irinotecan (10 and 20 μΜ) inhibit autophagy in microsatellite stable (MSS) CRC cell lines. The inhibition of autophagy in MSS CRC cell lines after treatment with oxaliplatin and irinotecan is further identified through monodancylcadaverine staining. Moreover, inhibition of autophagy with molecules such as hydroxychloroquine (20 μΜ) and 3-methyladenine (5 mM) was identified by the accumulation of p62 and LC3B.</p></sec><sec><title>Conclusions:</title><p>Beclin-1 is an independent prognostic factor of overall survival and PFS. Also, Rab-7 is identified as an independent prognostic factor of PFS. Besides, several chemotherapeutic drugs such as oxaliplatin and irinotecan inhibit autophagy in MSS CRC cell lines in a similar way like hydroxychloroquine and 3-methyladenine. Thus, in MSS patients who develop chemoresistance, a combination of other therapies that include an autophagy inhibitor could be more beneficial. Further clinical trials are needed to investigate these therapeutic strategies.</p></sec></abstract><kwd-group><title>Key Words:</title><kwd>autophagy</kwd><kwd>Beclin-1</kwd><kwd>chemotherapy</kwd><kwd>colorectal cancer</kwd></kwd-group><custom-meta-group><custom-meta><meta-name>SDC</meta-name><meta-value>T</meta-value></custom-meta><custom-meta><meta-name>OPEN-ACCESS</meta-name><meta-value>TRUE</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc><affiliations><list><country><li>Grèce</li></country><region><li>Attique (région)</li></region><settlement><li>Athènes</li></settlement></list><tree><noCountry><name sortKey="Chatziandreou, Ilenia" sort="Chatziandreou, Ilenia" uniqKey="Chatziandreou I" first="Ilenia" last="Chatziandreou">Ilenia Chatziandreou</name><name sortKey="Giannopoulou, Ioanna" sort="Giannopoulou, Ioanna" uniqKey="Giannopoulou I" first="Ioanna" last="Giannopoulou">Ioanna Giannopoulou</name><name sortKey="Koustas, Evangelos" sort="Koustas, Evangelos" uniqKey="Koustas E" first="Evangelos" last="Koustas">Evangelos Koustas</name><name sortKey="Kyriakopoulou, Georgia" sort="Kyriakopoulou, Georgia" uniqKey="Kyriakopoulou G" first="Georgia" last="Kyriakopoulou">Georgia Kyriakopoulou</name><name sortKey="Michelli, Maria" sort="Michelli, Maria" uniqKey="Michelli M" first="Maria" last="Michelli">Maria Michelli</name><name sortKey="Papavassiliou, Athanasios G" sort="Papavassiliou, Athanasios G" uniqKey="Papavassiliou A" first="Athanasios G." last="Papavassiliou">Athanasios G. Papavassiliou</name><name sortKey="Saetta, Angelica A" sort="Saetta, Angelica A" uniqKey="Saetta A" first="Angelica A." last="Saetta">Angelica A. Saetta</name><name sortKey="Sarantis, Panagiotis" sort="Sarantis, Panagiotis" uniqKey="Sarantis P" first="Panagiotis" last="Sarantis">Panagiotis Sarantis</name><name sortKey="Schizas, Dimitrios" sort="Schizas, Dimitrios" uniqKey="Schizas D" first="Dimitrios" last="Schizas">Dimitrios Schizas</name><name sortKey="Theoharis, Stamatios" sort="Theoharis, Stamatios" uniqKey="Theoharis S" first="Stamatios" last="Theoharis">Stamatios Theoharis</name></noCountry><country name="Grèce"><region name="Attique (région)"><name sortKey="Karamouzis, Michalis V" sort="Karamouzis, Michalis V" uniqKey="Karamouzis M" first="Michalis V." last="Karamouzis">Michalis V. Karamouzis</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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