Thyroid malignant neoplasm-associated biomarkers as targets for oncolytic virotherapy
Identifieur interne : 008755 ( Ncbi/Merge ); précédent : 008754; suivant : 008756Thyroid malignant neoplasm-associated biomarkers as targets for oncolytic virotherapy
Auteurs : Mingxu Guan [États-Unis] ; Yanping Ma ; Sahil Rajesh Shah [États-Unis] ; Gaetano Romano [États-Unis]Source :
- Oncolytic Virotherapy [ 2253-1572 ] ; 2016.
Abstract
Biomarkers associated with thyroid malignant neoplasm (TMN) have been widely applied in clinical diagnosis and in research oncological programs. The identification of novel TMN biomarkers has greatly improved the efficacy of clinical diagnosis. A more accurate diagnosis may lead to better clinical outcomes and effective treatments. However, the major deficiency of conventional chemotherapy and radiotherapy is lack of specificity. Due to the macrokinetic interactions, adverse side effects will occur, including chemotherapy and radiotherapy resistance. Therefore, a new treatment is urgently needed. As an alternative approach, oncolytic virotherapy may represent an opportunity for treatment strategies that can more specifically target tumor cells. In most cases, viral entry requires the expression of specific receptors on the surface of the host cell. Currently, molecular virologists and gene therapists are working on engineering oncolytic viruses with altered tropism for the specific targeting of malignant cells. This review focuses on the strategy of biomarkers for the production of novel TMN oncolytic therapeutics, which may improve the specificity of targeting of tumor cells and limit adverse effects in patients.
Url:
DOI: 10.2147/OV.S99856
PubMed: 27579295
PubMed Central: 4996252
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Thyroid malignant neoplasm-associated biomarkers as targets for oncolytic virotherapy</title><author><name sortKey="Guan, Mingxu" sort="Guan, Mingxu" uniqKey="Guan M" first="Mingxu" last="Guan">Mingxu Guan</name><affiliation wicri:level="1"><nlm:aff id="af1-ov-5-035">Virology, Research and Development, Zoetis Inc., Kalamazoo, MI, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Virology, Research and Development, Zoetis Inc., Kalamazoo, MI</wicri:regionArea><wicri:noRegion>MI</wicri:noRegion></affiliation></author><author><name sortKey="Ma, Yanping" sort="Ma, Yanping" uniqKey="Ma Y" first="Yanping" last="Ma">Yanping Ma</name><affiliation><nlm:aff id="af2-ov-5-035">Virology Laboratory, Shengjing Hospital, China Medical University, Shenyang, Liaoning, People’s Republic China</nlm:aff><wicri:noCountry code="subfield">People’s Republic China</wicri:noCountry></affiliation></author><author><name sortKey="Shah, Sahil Rajesh" sort="Shah, Sahil Rajesh" uniqKey="Shah S" first="Sahil Rajesh" last="Shah">Sahil Rajesh Shah</name><affiliation wicri:level="1"><nlm:aff id="af3-ov-5-035">Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA</wicri:regionArea><wicri:noRegion>PA</wicri:noRegion></affiliation></author><author><name sortKey="Romano, Gaetano" sort="Romano, Gaetano" uniqKey="Romano G" first="Gaetano" last="Romano">Gaetano Romano</name><affiliation wicri:level="1"><nlm:aff id="af3-ov-5-035">Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biology, College of Science and Technology, Temple University, Philadelphia, 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as targets for oncolytic virotherapy</title><author><name sortKey="Guan, Mingxu" sort="Guan, Mingxu" uniqKey="Guan M" first="Mingxu" last="Guan">Mingxu Guan</name><affiliation wicri:level="1"><nlm:aff id="af1-ov-5-035">Virology, Research and Development, Zoetis Inc., Kalamazoo, MI, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Virology, Research and Development, Zoetis Inc., Kalamazoo, MI</wicri:regionArea><wicri:noRegion>MI</wicri:noRegion></affiliation></author><author><name sortKey="Ma, Yanping" sort="Ma, Yanping" uniqKey="Ma Y" first="Yanping" last="Ma">Yanping Ma</name><affiliation><nlm:aff id="af2-ov-5-035">Virology Laboratory, Shengjing Hospital, China Medical University, Shenyang, Liaoning, People’s Republic China</nlm:aff><wicri:noCountry code="subfield">People’s Republic China</wicri:noCountry></affiliation></author><author><name sortKey="Shah, Sahil Rajesh" sort="Shah, Sahil Rajesh" uniqKey="Shah S" first="Sahil Rajesh" last="Shah">Sahil Rajesh Shah</name><affiliation wicri:level="1"><nlm:aff id="af3-ov-5-035">Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA</wicri:regionArea><wicri:noRegion>PA</wicri:noRegion></affiliation></author><author><name sortKey="Romano, Gaetano" sort="Romano, Gaetano" uniqKey="Romano G" first="Gaetano" last="Romano">Gaetano Romano</name><affiliation wicri:level="1"><nlm:aff id="af3-ov-5-035">Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA</wicri:regionArea><wicri:noRegion>PA</wicri:noRegion></affiliation></author></analytic><series><title level="j">Oncolytic Virotherapy</title><idno type="eISSN">2253-1572</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Biomarkers associated with thyroid malignant neoplasm (TMN) have been widely applied in clinical diagnosis and in research oncological programs. The identification of novel TMN biomarkers has greatly improved the efficacy of clinical diagnosis. A more accurate diagnosis may lead to better clinical outcomes and effective treatments. However, the major deficiency of conventional chemotherapy and radiotherapy is lack of specificity. Due to the macrokinetic interactions, adverse side effects will occur, including chemotherapy and radiotherapy resistance. Therefore, a new treatment is urgently needed. As an alternative approach, oncolytic virotherapy may represent an opportunity for treatment strategies that can more specifically target tumor cells. In most cases, viral entry requires the expression of specific receptors on the surface of the host cell. Currently, molecular virologists and gene therapists are working on engineering oncolytic viruses with altered tropism for the specific targeting of malignant cells. This review focuses on the strategy of biomarkers for the production of novel TMN oncolytic therapeutics, which may improve the specificity of targeting of tumor cells and limit adverse effects in patients.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Dean, Ds" uniqKey="Dean D">DS Dean</name></author><author><name sortKey="Gharib, H" uniqKey="Gharib H">H Gharib</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cunningham, Mp" uniqKey="Cunningham M">MP Cunningham</name></author><author><name sortKey="Duda, Rb" uniqKey="Duda R">RB Duda</name></author><author><name sortKey="Recant, W" uniqKey="Recant W">W Recant</name></author><author><name sortKey="Chmiel, Js" uniqKey="Chmiel J">JS Chmiel</name></author><author><name sortKey="Sylvester, Ja" uniqKey="Sylvester J">JA Sylvester</name></author><author><name sortKey="Fremgen, A" uniqKey="Fremgen A">A 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Oncolytic Virother</journal-id><journal-id journal-id-type="iso-abbrev">Oncolytic Virother</journal-id><journal-id journal-id-type="publisher-id">Oncolytic Virotherapy</journal-id><journal-title-group><journal-title>Oncolytic Virotherapy</journal-title></journal-title-group><issn pub-type="epub">2253-1572</issn><publisher><publisher-name>Dove Medical Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">27579295</article-id><article-id pub-id-type="pmc">4996252</article-id><article-id pub-id-type="doi">10.2147/OV.S99856</article-id><article-id pub-id-type="publisher-id">ov-5-035</article-id><article-categories><subj-group subj-group-type="heading"><subject>Review</subject></subj-group></article-categories><title-group><article-title>Thyroid malignant neoplasm-associated biomarkers as targets for oncolytic virotherapy</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Guan</surname><given-names>Mingxu</given-names></name><xref ref-type="aff" rid="af1-ov-5-035">1</xref><xref ref-type="corresp" rid="c1-ov-5-035"></xref></contrib><contrib contrib-type="author"><name><surname>Ma</surname><given-names>Yanping</given-names></name><xref ref-type="aff" rid="af2-ov-5-035">2</xref></contrib><contrib contrib-type="author"><name><surname>Shah</surname><given-names>Sahil Rajesh</given-names></name><xref ref-type="aff" rid="af3-ov-5-035">3</xref></contrib><contrib contrib-type="author"><name><surname>Romano</surname><given-names>Gaetano</given-names></name><xref ref-type="aff" rid="af3-ov-5-035">3</xref></contrib></contrib-group><aff id="af1-ov-5-035"><label>1</label>Virology, Research and Development, Zoetis Inc., Kalamazoo, MI, USA</aff><aff id="af2-ov-5-035"><label>2</label>Virology Laboratory, Shengjing Hospital, China Medical University, Shenyang, Liaoning, People’s Republic China</aff><aff id="af3-ov-5-035"><label>3</label>Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA, USA</aff><author-notes><corresp id="c1-ov-5-035">Correspondence: Mingxu Guan, Virology, Research and Development, Zoetis Inc., 333 Portage Street, Kalamazoo, MI 49007, USA, Email <email>mingxuguan@gmail.com</email></corresp></author-notes><pub-date pub-type="collection"><year>2016</year></pub-date><pub-date pub-type="epub"><day>21</day><month>6</month><year>2016</year></pub-date><volume>5</volume><fpage>35</fpage><lpage>43</lpage><permissions><copyright-statement>© 2016 Guan et al. This work is published and licensed by Dove Medical Press Limited</copyright-statement><copyright-year>2016</copyright-year><license><license-p>The full terms of this license are available at <ext-link ext-link-type="uri" xlink:href="https://www.dovepress.com/terms.php">https://www.dovepress.com/terms.php</ext-link> and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc/3.0/">http://creativecommons.org/licenses/by-nc/3.0/</ext-link>). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.</license-p></license></permissions><abstract><p>Biomarkers associated with thyroid malignant neoplasm (TMN) have been widely applied in clinical diagnosis and in research oncological programs. The identification of novel TMN biomarkers has greatly improved the efficacy of clinical diagnosis. A more accurate diagnosis may lead to better clinical outcomes and effective treatments. However, the major deficiency of conventional chemotherapy and radiotherapy is lack of specificity. Due to the macrokinetic interactions, adverse side effects will occur, including chemotherapy and radiotherapy resistance. Therefore, a new treatment is urgently needed. As an alternative approach, oncolytic virotherapy may represent an opportunity for treatment strategies that can more specifically target tumor cells. In most cases, viral entry requires the expression of specific receptors on the surface of the host cell. Currently, molecular virologists and gene therapists are working on engineering oncolytic viruses with altered tropism for the specific targeting of malignant cells. This review focuses on the strategy of biomarkers for the production of novel TMN oncolytic therapeutics, which may improve the specificity of targeting of tumor cells and limit adverse effects in patients.</p></abstract><kwd-group><title>Keywords</title><kwd>thyroid malignancy neoplasm</kwd><kwd>biomarkers</kwd><kwd>oncolytic virotherapy</kwd></kwd-group></article-meta></front><floats-group><fig id="f1-ov-5-035" position="float"><label>Figure 1</label><caption><p>Oncolytic viral tropism altered by modification of viral surface proteins.</p><p><bold>Notes:</bold> The modified virus binds with thyroid cell membrane biomarkers including TSHR, TPO, NIS, CD44, CD133, CAV-1, or Galectin-3. (<bold>A</bold>) TSH <italic>β</italic> subunit on the selected oncolytic virus for specific binding TSHR on thyroid cells. (<bold>B</bold>) Expression of specific antibodies against the thyroid membrane-bound biomarkers. (<bold>C</bold>) Expression of peptide aptamers that specifically target the TMN biomarkers on the thyroid follicular cells.</p><p><bold>Abbreviations:</bold> CAV-1, Caveolin-1; NIS, sodium/iodide symporter; CD, cluster of differentiation; LGAL3, galectin-3; TMN, thyroid malignant neoplasm; TPO, thyroid peroxidase; TSHR, thyrotropin receptor.</p></caption><graphic xlink:href="ov-5-035Fig1"></graphic></fig><table-wrap id="t1-ov-5-035" position="float"><label>Table 1</label><caption><p>Estimated protein expression of TMN biomarkers</p></caption><table frame="hsides" rules="groups"><thead><tr><th colspan="11" valign="top" align="left" rowspan="1">Estimated protein expression log<sub>10</sub> (ppm)</th></tr><tr><th colspan="11" align="left" valign="bottom" rowspan="1"><hr></hr></th></tr><tr><th valign="top" align="left" rowspan="1" colspan="1">Biomarker</th><th valign="top" align="left" rowspan="1" colspan="1">Serum</th><th valign="top" align="left" rowspan="1" colspan="1">Plasma</th><th valign="top" align="left" rowspan="1" colspan="1">Platelet</th><th valign="top" align="left" rowspan="1" colspan="1">Liver</th><th valign="top" align="left" rowspan="1" colspan="1">Heart</th><th valign="top" align="left" rowspan="1" colspan="1">Lung</th><th valign="top" align="left" rowspan="1" colspan="1">Brain</th><th valign="top" align="left" rowspan="1" colspan="1">Kidney</th><th valign="top" align="left" rowspan="1" colspan="1">Pancreas</th><th valign="top" align="left" rowspan="1" colspan="1">Adipocyte</th></tr></thead><tbody><tr><td valign="top" align="left" rowspan="1" colspan="1">TSHR</td><td valign="top" align="left" rowspan="1" colspan="1">–</td><td valign="top" align="left" rowspan="1" colspan="1">1</td><td valign="top" align="left" rowspan="1" colspan="1">>0</td><td valign="top" align="left" rowspan="1" colspan="1">–</td><td valign="top" align="left" rowspan="1" colspan="1">–</td><td valign="top" align="left" rowspan="1" colspan="1">–</td><td valign="top" align="left" rowspan="1" colspan="1">0</td><td valign="top" align="left" rowspan="1" colspan="1">–</td><td valign="top" align="left" rowspan="1" colspan="1">–</td><td valign="top" align="left" rowspan="1" colspan="1">–</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">TPO</td><td valign="top" align="left" rowspan="1" colspan="1">–</td><td valign="top" align="left" rowspan="1" colspan="1">>1</td><td valign="top" align="left" rowspan="1" colspan="1">>−1</td><td valign="top" align="left" rowspan="1" colspan="1"><1</td><td valign="top" align="left" rowspan="1" colspan="1">1</td><td valign="top" align="left" rowspan="1" colspan="1">–</td><td valign="top" align="left" rowspan="1" colspan="1">–</td><td valign="top" align="left" rowspan="1" colspan="1">–</td><td valign="top" align="left" rowspan="1" colspan="1">–</td><td valign="top" align="left" rowspan="1" colspan="1">–</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">NIS</td><td valign="top" align="left" rowspan="1" colspan="1">–</td><td valign="top" align="left" rowspan="1" colspan="1">1</td><td valign="top" align="left" rowspan="1" colspan="1">–</td><td valign="top" align="left" rowspan="1" colspan="1">–</td><td valign="top" align="left" rowspan="1" colspan="1">–</td><td valign="top" align="left" rowspan="1" colspan="1">–</td><td valign="top" align="left" rowspan="1" colspan="1">–</td><td valign="top" align="left" rowspan="1" colspan="1">–</td><td valign="top" align="left" rowspan="1" colspan="1">–</td><td valign="top" align="left" rowspan="1" colspan="1">–</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">CD133</td><td valign="top" align="left" rowspan="1" colspan="1">–</td><td valign="top" align="left" rowspan="1" colspan="1"><1</td><td valign="top" align="left" rowspan="1" colspan="1">0</td><td valign="top" align="left" rowspan="1" colspan="1">–</td><td valign="top" align="left" rowspan="1" colspan="1">–</td><td valign="top" align="left" rowspan="1" colspan="1">2</td><td valign="top" align="left" rowspan="1" colspan="1">–</td><td valign="top" align="left" rowspan="1" colspan="1">–</td><td valign="top" align="left" rowspan="1" colspan="1">–</td><td valign="top" align="left" rowspan="1" colspan="1">–</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">CD44</td><td valign="top" align="left" rowspan="1" colspan="1">2</td><td valign="top" align="left" rowspan="1" colspan="1"><1</td><td valign="top" align="left" rowspan="1" colspan="1"><1</td><td valign="top" align="left" rowspan="1" colspan="1">>3</td><td valign="top" align="left" rowspan="1" colspan="1">>2</td><td valign="top" align="left" rowspan="1" colspan="1">2</td><td valign="top" align="left" rowspan="1" colspan="1"><1</td><td valign="top" align="left" rowspan="1" colspan="1">>0</td><td valign="top" align="left" rowspan="1" colspan="1">3</td><td valign="top" align="left" rowspan="1" colspan="1">–</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">CAV-1</td><td valign="top" align="left" rowspan="1" colspan="1">–</td><td valign="top" align="left" rowspan="1" colspan="1">–</td><td valign="top" align="left" rowspan="1" colspan="1">0</td><td valign="top" align="left" rowspan="1" colspan="1">1</td><td valign="top" align="left" rowspan="1" colspan="1">3</td><td valign="top" align="left" rowspan="1" colspan="1">>2</td><td valign="top" align="left" rowspan="1" colspan="1">–</td><td valign="top" align="left" rowspan="1" colspan="1">2</td><td valign="top" align="left" rowspan="1" colspan="1">–</td><td valign="top" align="left" rowspan="1" colspan="1">4</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">LGAL3</td><td valign="top" align="left" rowspan="1" colspan="1">–</td><td valign="top" align="left" rowspan="1" colspan="1"><1</td><td valign="top" align="left" rowspan="1" colspan="1">>1</td><td valign="top" align="left" rowspan="1" colspan="1">–</td><td valign="top" align="left" rowspan="1" colspan="1"><3</td><td valign="top" align="left" rowspan="1" colspan="1">>1</td><td valign="top" align="left" rowspan="1" colspan="1">2</td><td valign="top" align="left" rowspan="1" colspan="1">>1</td><td valign="top" align="left" rowspan="1" colspan="1">–</td><td valign="top" align="left" rowspan="1" colspan="1">–</td></tr></tbody></table><table-wrap-foot><fn id="tfn1-ov-5-035"><p><bold>Note:</bold> – indicates that the value is below zero as reported by Safran et al.<xref rid="b10-ov-5-035" ref-type="bibr">10</xref></p></fn><fn id="tfn2-ov-5-035"><p><bold>Abbreviations:</bold> CAV-1, Caveolin-1; NIS, sodium/iodide symporter; CD, cluster of differentiation; LGAL3, galectin-3; ppm, parts per million; TMN, thyroid malignant neoplasm; TPO, thyroid peroxidase; TSHR, thyrotropin receptor.</p></fn></table-wrap-foot></table-wrap><table-wrap id="t2-ov-5-035" position="float"><label>Table 2</label><caption><p>TMN biomarkers in subcellular locations</p></caption><table frame="hsides" rules="groups"><thead><tr><th rowspan="2" valign="top" align="left" colspan="1">Biomarker</th><th colspan="9" valign="top" align="left" rowspan="1">Subcellular locations from compartment and confidence number from 0 to 5<xref ref-type="table-fn" rid="tfn3-ov-5-035">a</xref><hr></hr></th></tr><tr><th valign="top" align="left" rowspan="1" colspan="1">Extracellular</th><th valign="top" align="left" rowspan="1" colspan="1">Plasma</th><th valign="top" align="left" rowspan="1" colspan="1">Cytosol</th><th valign="top" align="left" rowspan="1" colspan="1">Nucleus endoplasmic</th><th valign="top" align="left" rowspan="1" colspan="1">Endosome</th><th valign="top" align="left" rowspan="1" colspan="1">Golgi lysosome</th><th valign="top" align="left" rowspan="1" colspan="1">Mitochondrion</th><th valign="top" align="left" rowspan="1" colspan="1">Space membrane</th><th valign="top" align="left" rowspan="1" colspan="1">Reticulum apparatus</th></tr></thead><tbody><tr><td valign="top" align="left" rowspan="1" colspan="1">TSHR</td><td valign="top" align="left" rowspan="1" colspan="1">1</td><td valign="top" align="left" rowspan="1" colspan="1">2</td><td valign="top" align="left" rowspan="1" colspan="1">5</td><td valign="top" align="left" rowspan="1" colspan="1">1</td><td valign="top" align="left" rowspan="1" colspan="1">1</td><td valign="top" align="left" rowspan="1" colspan="1">0</td><td valign="top" align="left" rowspan="1" colspan="1">0</td><td valign="top" align="left" rowspan="1" colspan="1">0</td><td valign="top" align="left" rowspan="1" colspan="1">0</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">TPO</td><td valign="top" align="left" rowspan="1" colspan="1">2</td><td valign="top" align="left" rowspan="1" colspan="1">4</td><td valign="top" align="left" rowspan="1" colspan="1">2</td><td valign="top" align="left" rowspan="1" colspan="1">2</td><td valign="top" align="left" rowspan="1" colspan="1">2</td><td valign="top" align="left" rowspan="1" colspan="1">2</td><td valign="top" align="left" rowspan="1" colspan="1">2</td><td valign="top" align="left" rowspan="1" colspan="1">1</td><td valign="top" align="left" rowspan="1" colspan="1">2</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">NIS</td><td valign="top" align="left" rowspan="1" colspan="1">4</td><td valign="top" align="left" rowspan="1" colspan="1">4</td><td valign="top" align="left" rowspan="1" colspan="1">0</td><td valign="top" align="left" rowspan="1" colspan="1">5</td><td valign="top" align="left" rowspan="1" colspan="1">0</td><td valign="top" align="left" rowspan="1" colspan="1">0</td><td valign="top" align="left" rowspan="1" colspan="1">0</td><td valign="top" align="left" rowspan="1" colspan="1">0</td><td valign="top" align="left" rowspan="1" colspan="1">0</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">CD133</td><td valign="top" align="left" rowspan="1" colspan="1">2</td><td valign="top" align="left" rowspan="1" colspan="1">5</td><td valign="top" align="left" rowspan="1" colspan="1">1</td><td valign="top" align="left" rowspan="1" colspan="1">2</td><td valign="top" align="left" rowspan="1" colspan="1">1</td><td valign="top" align="left" rowspan="1" colspan="1">0</td><td valign="top" align="left" rowspan="1" colspan="1">0</td><td valign="top" align="left" rowspan="1" colspan="1">0</td><td valign="top" align="left" rowspan="1" colspan="1">0</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">CD44</td><td valign="top" align="left" rowspan="1" colspan="1">3</td><td valign="top" align="left" rowspan="1" colspan="1">5</td><td valign="top" align="left" rowspan="1" colspan="1">0</td><td valign="top" align="left" rowspan="1" colspan="1">2</td><td valign="top" align="left" rowspan="1" colspan="1">1</td><td valign="top" align="left" rowspan="1" colspan="1">1</td><td valign="top" align="left" rowspan="1" colspan="1">4</td><td valign="top" align="left" rowspan="1" colspan="1">0</td><td valign="top" align="left" rowspan="1" colspan="1">1</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">CAV-1</td><td valign="top" align="left" rowspan="1" colspan="1">2</td><td valign="top" align="left" rowspan="1" colspan="1">5</td><td valign="top" align="left" rowspan="1" colspan="1">2</td><td valign="top" align="left" rowspan="1" colspan="1">2</td><td valign="top" align="left" rowspan="1" colspan="1">5</td><td valign="top" align="left" rowspan="1" colspan="1">5</td><td valign="top" align="left" rowspan="1" colspan="1">5</td><td valign="top" align="left" rowspan="1" colspan="1">1</td><td valign="top" align="left" rowspan="1" colspan="1">1</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">LGAL3</td><td valign="top" align="left" rowspan="1" colspan="1">5</td><td valign="top" align="left" rowspan="1" colspan="1">4</td><td valign="top" align="left" rowspan="1" colspan="1">3</td><td valign="top" align="left" rowspan="1" colspan="1">5</td><td valign="top" align="left" rowspan="1" colspan="1">0</td><td valign="top" align="left" rowspan="1" colspan="1">1</td><td valign="top" align="left" rowspan="1" colspan="1">0</td><td valign="top" align="left" rowspan="1" colspan="1">1</td><td valign="top" align="left" rowspan="1" colspan="1">5</td></tr></tbody></table><table-wrap-foot><fn><p><bold>Notes:</bold></p></fn><fn id="tfn3-ov-5-035"><label>a</label><p>Confidence number 0–5: It graphically summarizes the types of evidence supporting the localization by Binder et al.<xref rid="b11-ov-5-035" ref-type="bibr">11</xref></p></fn><fn id="tfn4-ov-5-035"><p><bold>Abbreviations:</bold> CAV-1, caveolin-1; NIS, sodium/iodide symporter; CD, cluster of differentiation; LGAL3, galectin-3; TMN, thyroid malignant neoplasm; TPO, thyroid peroxidase; TSHR, thyrotropin receptor.</p></fn></table-wrap-foot></table-wrap></floats-group></pmc><affiliations><list><country><li>États-Unis</li></country></list><tree><noCountry><name sortKey="Ma, Yanping" sort="Ma, Yanping" uniqKey="Ma Y" 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