Expression of Angiopoietin-2 and Vascular Endothelial Growth Factor Receptor-3 Correlates with Lymphangiogenesis and Angiogenesis and Affects Survival of Oral Squamous Cell Carcinoma
Identifieur interne : 002340 ( Pmc/Checkpoint ); précédent : 002339; suivant : 002341Expression of Angiopoietin-2 and Vascular Endothelial Growth Factor Receptor-3 Correlates with Lymphangiogenesis and Angiogenesis and Affects Survival of Oral Squamous Cell Carcinoma
Auteurs : Chao Li [République populaire de Chine] ; Jinchuan Fan [République populaire de Chine] ; Xicheng Song [République populaire de Chine] ; Bing Zhang [République populaire de Chine] ; Yu Chen [République populaire de Chine] ; Chunhua Li [République populaire de Chine] ; Kun Mi [République populaire de Chine] ; Hong Ma [République populaire de Chine] ; Yufeng Song [République populaire de Chine] ; Xiaofeng Tao [République populaire de Chine] ; Guojun Li [États-Unis]Source :
- PLoS ONE [ 1932-6203 ] ; 2013.
Abstract
Both Ang-2 and VEGFR-3 are major regulators of angiogenesis and lymphangiogenesis, respectively, and thus may affect prognosis of OSCC. We sought to determine the associations between Ang-2 and VEGFR-3 expression and survival of OSCC.
Ang-2 and VEGFR-3 expression was determined immunohistochemically in tumor tissues from 112 patients with OSCC; OSCC-adjacent noncancerous oral tissue from 85 OSCC patients; and normal oral mucosa from 37 cancer-free individuals. A log-rank test and Cox proportional hazard models were used to compare survival among different groups with expression of Ang-2 and VEGFR-3.
Ang-2 and VEGFR-3 expression was upregulated in OSCC compared to nontumor tissue (all
These results suggest that increased expression in tumors of Ang-2 may individually, or in combination with VEGFR-3, predict poor prognosis of OSCC.
Url:
DOI: 10.1371/journal.pone.0075388
PubMed: 24040410
PubMed Central: 3770542
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Expression of Angiopoietin-2 and Vascular Endothelial Growth Factor Receptor-3 Correlates with Lymphangiogenesis and Angiogenesis and Affects Survival of Oral Squamous Cell Carcinoma</title><author><name sortKey="Li, Chao" sort="Li, Chao" uniqKey="Li C" first="Chao" last="Li">Chao Li</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Head and Neck Surgery, Sichuan Cancer Hospital, Chengdu, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Head and Neck Surgery, Sichuan Cancer Hospital, Chengdu</wicri:regionArea><wicri:noRegion>Chengdu</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>State Key Laboratory of Oral Diseases in Sichuan University, Sichuan, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Oral Diseases in Sichuan University, Sichuan</wicri:regionArea><wicri:noRegion>Sichuan</wicri:noRegion></affiliation></author><author><name sortKey="Fan, Jinchuan" sort="Fan, Jinchuan" uniqKey="Fan J" first="Jinchuan" last="Fan">Jinchuan Fan</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Head and Neck Surgery, Sichuan Cancer Hospital, Chengdu, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Head and Neck Surgery, Sichuan Cancer Hospital, Chengdu</wicri:regionArea><wicri:noRegion>Chengdu</wicri:noRegion></affiliation></author><author><name sortKey="Song, Xicheng" sort="Song, Xicheng" uniqKey="Song X" first="Xicheng" last="Song">Xicheng Song</name><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Department of Otorhinolaryngology Head and Neck Surgery, Yuhuangding Hospital, Qingdao University, Yantai, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Otorhinolaryngology Head and Neck Surgery, Yuhuangding Hospital, Qingdao University, Yantai</wicri:regionArea><wicri:noRegion>Yantai</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Bing" sort="Zhang, Bing" uniqKey="Zhang B" first="Bing" last="Zhang">Bing Zhang</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Head and Neck Surgery, Sichuan Cancer Hospital, Chengdu, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Head and Neck Surgery, Sichuan Cancer Hospital, Chengdu</wicri:regionArea><wicri:noRegion>Chengdu</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Yu" sort="Chen, Yu" uniqKey="Chen Y" first="Yu" last="Chen">Yu Chen</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>State Key Laboratory of Oral Diseases in Sichuan University, Sichuan, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Oral Diseases in Sichuan University, Sichuan</wicri:regionArea><wicri:noRegion>Sichuan</wicri:noRegion></affiliation></author><author><name sortKey="Li, Chunhua" sort="Li, Chunhua" uniqKey="Li C" first="Chunhua" last="Li">Chunhua Li</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Head and Neck Surgery, Sichuan Cancer Hospital, Chengdu, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Head and Neck Surgery, Sichuan Cancer Hospital, Chengdu</wicri:regionArea><wicri:noRegion>Chengdu</wicri:noRegion></affiliation></author><author><name sortKey="Mi, Kun" sort="Mi, Kun" uniqKey="Mi K" first="Kun" last="Mi">Kun Mi</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Head and Neck Surgery, Sichuan Cancer Hospital, Chengdu, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Head and Neck Surgery, Sichuan Cancer Hospital, Chengdu</wicri:regionArea><wicri:noRegion>Chengdu</wicri:noRegion></affiliation></author><author><name sortKey="Ma, Hong" sort="Ma, Hong" uniqKey="Ma H" first="Hong" last="Ma">Hong Ma</name><affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>Department of Oral and Maxillary Surgery, the Affiliated Hospital of Guiyang Medical College, Guiyang, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Oral and Maxillary Surgery, the Affiliated Hospital of Guiyang Medical College, Guiyang</wicri:regionArea><wicri:noRegion>Guiyang</wicri:noRegion></affiliation></author><author><name sortKey="Song, Yufeng" sort="Song, Yufeng" uniqKey="Song Y" first="Yufeng" last="Song">Yufeng Song</name><affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>Department of Oral and Maxillary Surgery, the Affiliated Hospital of Guiyang Medical College, Guiyang, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Oral and Maxillary Surgery, the Affiliated Hospital of Guiyang Medical College, Guiyang</wicri:regionArea><wicri:noRegion>Guiyang</wicri:noRegion></affiliation></author><author><name sortKey="Tao, Xiaofeng" sort="Tao, Xiaofeng" uniqKey="Tao X" first="Xiaofeng" last="Tao">Xiaofeng Tao</name><affiliation wicri:level="1"><nlm:aff id="aff5"><addr-line>Radiology Department of Shanghai Ninth People's Hospital Affiliated Shanghai JIaoTong University School of Medicine, Shanghai, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Radiology Department of Shanghai Ninth People's Hospital Affiliated Shanghai JIaoTong University School of Medicine, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Li, Guojun" sort="Li, Guojun" uniqKey="Li G" first="Guojun" last="Li">Guojun Li</name><affiliation wicri:level="2"><nlm:aff id="aff6"><addr-line>Department of Head and Neck Surgery, U.T. M.D. Anderson Cancer Center, Houston, Texas, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Head and Neck Surgery, U.T. M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24040410</idno><idno type="pmc">3770542</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3770542</idno><idno type="RBID">PMC:3770542</idno><idno type="doi">10.1371/journal.pone.0075388</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">004486</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">004486</idno><idno type="wicri:Area/Pmc/Curation">004485</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">004485</idno><idno type="wicri:Area/Pmc/Checkpoint">002340</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">002340</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Expression of Angiopoietin-2 and Vascular Endothelial Growth Factor Receptor-3 Correlates with Lymphangiogenesis and Angiogenesis and Affects Survival of Oral Squamous Cell Carcinoma</title><author><name sortKey="Li, Chao" sort="Li, Chao" uniqKey="Li C" first="Chao" last="Li">Chao Li</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Head and Neck Surgery, Sichuan Cancer Hospital, Chengdu, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Head and Neck Surgery, Sichuan Cancer Hospital, Chengdu</wicri:regionArea><wicri:noRegion>Chengdu</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>State Key Laboratory of Oral Diseases in Sichuan University, Sichuan, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Oral Diseases in Sichuan University, Sichuan</wicri:regionArea><wicri:noRegion>Sichuan</wicri:noRegion></affiliation></author><author><name sortKey="Fan, Jinchuan" sort="Fan, Jinchuan" uniqKey="Fan J" first="Jinchuan" last="Fan">Jinchuan Fan</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Head and Neck Surgery, Sichuan Cancer Hospital, Chengdu, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Head and Neck Surgery, Sichuan Cancer Hospital, Chengdu</wicri:regionArea><wicri:noRegion>Chengdu</wicri:noRegion></affiliation></author><author><name sortKey="Song, Xicheng" sort="Song, Xicheng" uniqKey="Song X" first="Xicheng" last="Song">Xicheng Song</name><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Department of Otorhinolaryngology Head and Neck Surgery, Yuhuangding Hospital, Qingdao University, Yantai, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Otorhinolaryngology Head and Neck Surgery, Yuhuangding Hospital, Qingdao University, Yantai</wicri:regionArea><wicri:noRegion>Yantai</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Bing" sort="Zhang, Bing" uniqKey="Zhang B" first="Bing" last="Zhang">Bing Zhang</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Head and Neck Surgery, Sichuan Cancer Hospital, Chengdu, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Head and Neck Surgery, Sichuan Cancer Hospital, Chengdu</wicri:regionArea><wicri:noRegion>Chengdu</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Yu" sort="Chen, Yu" uniqKey="Chen Y" first="Yu" last="Chen">Yu Chen</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>State Key Laboratory of Oral Diseases in Sichuan University, Sichuan, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Oral Diseases in Sichuan University, Sichuan</wicri:regionArea><wicri:noRegion>Sichuan</wicri:noRegion></affiliation></author><author><name sortKey="Li, Chunhua" sort="Li, Chunhua" uniqKey="Li C" first="Chunhua" last="Li">Chunhua Li</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Head and Neck Surgery, Sichuan Cancer Hospital, Chengdu, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Head and Neck Surgery, Sichuan Cancer Hospital, Chengdu</wicri:regionArea><wicri:noRegion>Chengdu</wicri:noRegion></affiliation></author><author><name sortKey="Mi, Kun" sort="Mi, Kun" uniqKey="Mi K" first="Kun" last="Mi">Kun Mi</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Head and Neck Surgery, Sichuan Cancer Hospital, Chengdu, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Head and Neck Surgery, Sichuan Cancer Hospital, Chengdu</wicri:regionArea><wicri:noRegion>Chengdu</wicri:noRegion></affiliation></author><author><name sortKey="Ma, Hong" sort="Ma, Hong" uniqKey="Ma H" first="Hong" last="Ma">Hong Ma</name><affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>Department of Oral and Maxillary Surgery, the Affiliated Hospital of Guiyang Medical College, Guiyang, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Oral and Maxillary Surgery, the Affiliated Hospital of Guiyang Medical College, Guiyang</wicri:regionArea><wicri:noRegion>Guiyang</wicri:noRegion></affiliation></author><author><name sortKey="Song, Yufeng" sort="Song, Yufeng" uniqKey="Song Y" first="Yufeng" last="Song">Yufeng Song</name><affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>Department of Oral and Maxillary Surgery, the Affiliated Hospital of Guiyang Medical College, Guiyang, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Oral and Maxillary Surgery, the Affiliated Hospital of Guiyang Medical College, Guiyang</wicri:regionArea><wicri:noRegion>Guiyang</wicri:noRegion></affiliation></author><author><name sortKey="Tao, Xiaofeng" sort="Tao, Xiaofeng" uniqKey="Tao X" first="Xiaofeng" last="Tao">Xiaofeng Tao</name><affiliation wicri:level="1"><nlm:aff id="aff5"><addr-line>Radiology Department of Shanghai Ninth People's Hospital Affiliated Shanghai JIaoTong University School of Medicine, Shanghai, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Radiology Department of Shanghai Ninth People's Hospital Affiliated Shanghai JIaoTong University School of Medicine, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Li, Guojun" sort="Li, Guojun" uniqKey="Li G" first="Guojun" last="Li">Guojun Li</name><affiliation wicri:level="2"><nlm:aff id="aff6"><addr-line>Department of Head and Neck Surgery, U.T. M.D. Anderson Cancer Center, Houston, Texas, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Head and Neck Surgery, U.T. M.D. Anderson Cancer Center, Houston, Texas</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Both Ang-2 and VEGFR-3 are major regulators of angiogenesis and lymphangiogenesis, respectively, and thus may affect prognosis of OSCC. We sought to determine the associations between Ang-2 and VEGFR-3 expression and survival of OSCC.</p></sec><sec><title>Methods</title><p>Ang-2 and VEGFR-3 expression was determined immunohistochemically in tumor tissues from 112 patients with OSCC; OSCC-adjacent noncancerous oral tissue from 85 OSCC patients; and normal oral mucosa from 37 cancer-free individuals. A log-rank test and Cox proportional hazard models were used to compare survival among different groups with expression of Ang-2 and VEGFR-3.</p></sec><sec><title>Results</title><p>Ang-2 and VEGFR-3 expression was upregulated in OSCC compared to nontumor tissue (all <italic>P</italic><0.05). High Ang-2 expression positively correlated with microvessel density (MVD) (<italic>P</italic><0.01), and high VEGFR-3 expression positively correlated with lymph node metastasis (<italic>P</italic><0.01) and lymphatic vessel density (LVD) (<italic>P</italic><0.01). The patients with high expression of Ang-2 alone or in combination with VEGFR-3 had a significantly worse survival than in patients with low expression of Ang-2 or any other co-expression status (all <italic>P</italic><0.05), respectively. Furthermore, multivariable analysis showed that patients with high expression of Ang-2 alone or in combination with VEGFR-3 had a significantly increased risk of death compared with those with low expression of Ang-2 or any other co-expression status (HR, 2.7, 95% CI, 1.1–6.2 and 5.0, 1.3–15.4, respectively).</p></sec><sec><title>Conclusions</title><p>These results suggest that increased expression in tumors of Ang-2 may individually, or in combination with VEGFR-3, predict poor prognosis of OSCC.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Massano, J" uniqKey="Massano J">J Massano</name></author><author><name sortKey="Regateiro, Fs" uniqKey="Regateiro F">FS Regateiro</name></author><author><name sortKey="Januario, G" uniqKey="Januario G">G Januário</name></author><author><name sortKey="Ferreira, A" uniqKey="Ferreira A">A Ferreira</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gale, 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<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS One</journal-id><journal-id journal-id-type="iso-abbrev">PLoS ONE</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">plosone</journal-id><journal-title-group><journal-title>PLoS ONE</journal-title></journal-title-group><issn pub-type="epub">1932-6203</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">24040410</article-id><article-id pub-id-type="pmc">3770542</article-id><article-id pub-id-type="publisher-id">PONE-D-13-01702</article-id><article-id pub-id-type="doi">10.1371/journal.pone.0075388</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title>Expression of Angiopoietin-2 and Vascular Endothelial Growth Factor Receptor-3 Correlates with Lymphangiogenesis and Angiogenesis and Affects Survival of Oral Squamous Cell Carcinoma</article-title><alt-title alt-title-type="running-head">Ang-2 and VEGFR-3 in OSCC Survival</alt-title></title-group><contrib-group><contrib contrib-type="author" equal-contrib="yes"><name><surname>Li</surname><given-names>Chao</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Fan</surname><given-names>Jinchuan</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Song</surname><given-names>Xicheng</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Zhang</surname><given-names>Bing</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Yu</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Li</surname><given-names>Chunhua</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Mi</surname><given-names>Kun</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ma</surname><given-names>Hong</given-names></name><xref ref-type="aff" rid="aff4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Song</surname><given-names>Yufeng</given-names></name><xref ref-type="aff" rid="aff4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Tao</surname><given-names>Xiaofeng</given-names></name><xref ref-type="aff" rid="aff5"><sup>5</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib><contrib contrib-type="author"><name><surname>Li</surname><given-names>Guojun</given-names></name><xref ref-type="aff" rid="aff6"><sup>6</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib></contrib-group><aff id="aff1"><label>1</label><addr-line>Department of Head and Neck Surgery, Sichuan Cancer Hospital, Chengdu, China</addr-line></aff><aff id="aff2"><label>2</label><addr-line>State Key Laboratory of Oral Diseases in Sichuan University, Sichuan, China</addr-line></aff><aff id="aff3"><label>3</label><addr-line>Department of Otorhinolaryngology Head and Neck Surgery, Yuhuangding Hospital, Qingdao University, Yantai, China</addr-line></aff><aff id="aff4"><label>4</label><addr-line>Department of Oral and Maxillary Surgery, the Affiliated Hospital of Guiyang Medical College, Guiyang, China</addr-line></aff><aff id="aff5"><label>5</label><addr-line>Radiology Department of Shanghai Ninth People's Hospital Affiliated Shanghai JIaoTong University School of Medicine, Shanghai, China</addr-line></aff><aff id="aff6"><label>6</label><addr-line>Department of Head and Neck Surgery, U.T. M.D. Anderson Cancer Center, Houston, Texas, United States of America</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>Srivastava</surname><given-names>Rakesh K.</given-names></name><role>Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1"><addr-line>The University of Kansas Medical center, United States of America</addr-line></aff><author-notes><corresp id="cor1">* E-mail: <email>gli@mdanderson.org</email> (GJL); <email>cjr.taoxiaofeng.@vip.163.com</email> (XFT)</corresp><fn fn-type="conflict"><p><bold>Competing Interests: </bold>The authors have declared that no competing interests exist.</p></fn><fn fn-type="con"><p>Conceived and designed the experiments: CL BZ GJL XFT. Performed the experiments: CL XCS BZ CHL KM. Analyzed the data: XCS HM YFS. Contributed reagents/materials/analysis tools: CL BZ GJL XFT JCF YC. Wrote the paper: CL BZ GJL XFT.</p></fn></author-notes><pub-date pub-type="collection"><year>2013</year></pub-date><pub-date pub-type="epub"><day>11</day><month>9</month><year>2013</year></pub-date><volume>8</volume><issue>9</issue><elocation-id>e75388</elocation-id><history><date date-type="received"><day>9</day><month>1</month><year>2013</year></date><date date-type="accepted"><day>15</day><month>8</month><year>2013</year></date></history><permissions><copyright-year>2013</copyright-year><copyright-holder>Li et al</copyright-holder><license><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p></license></permissions><abstract><sec><title>Background</title><p>Both Ang-2 and VEGFR-3 are major regulators of angiogenesis and lymphangiogenesis, respectively, and thus may affect prognosis of OSCC. We sought to determine the associations between Ang-2 and VEGFR-3 expression and survival of OSCC.</p></sec><sec><title>Methods</title><p>Ang-2 and VEGFR-3 expression was determined immunohistochemically in tumor tissues from 112 patients with OSCC; OSCC-adjacent noncancerous oral tissue from 85 OSCC patients; and normal oral mucosa from 37 cancer-free individuals. A log-rank test and Cox proportional hazard models were used to compare survival among different groups with expression of Ang-2 and VEGFR-3.</p></sec><sec><title>Results</title><p>Ang-2 and VEGFR-3 expression was upregulated in OSCC compared to nontumor tissue (all <italic>P</italic><0.05). High Ang-2 expression positively correlated with microvessel density (MVD) (<italic>P</italic><0.01), and high VEGFR-3 expression positively correlated with lymph node metastasis (<italic>P</italic><0.01) and lymphatic vessel density (LVD) (<italic>P</italic><0.01). The patients with high expression of Ang-2 alone or in combination with VEGFR-3 had a significantly worse survival than in patients with low expression of Ang-2 or any other co-expression status (all <italic>P</italic><0.05), respectively. Furthermore, multivariable analysis showed that patients with high expression of Ang-2 alone or in combination with VEGFR-3 had a significantly increased risk of death compared with those with low expression of Ang-2 or any other co-expression status (HR, 2.7, 95% CI, 1.1–6.2 and 5.0, 1.3–15.4, respectively).</p></sec><sec><title>Conclusions</title><p>These results suggest that increased expression in tumors of Ang-2 may individually, or in combination with VEGFR-3, predict poor prognosis of OSCC.</p></sec></abstract><funding-group><funding-statement>The work was supported by grants from the Sichuan Provincial Bureau of Health, No. 080390 and No. 100572; Sichuan Provincial Science and Technology Department, No. 2009JY0093 and No. 11ZC0323. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement></funding-group><counts><page-count count="8"></page-count></counts></article-meta></front></pmc><affiliations><list><country><li>République populaire de Chine</li><li>États-Unis</li></country><region><li>Texas</li></region></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Li, Chao" sort="Li, Chao" uniqKey="Li C" first="Chao" last="Li">Chao Li</name></noRegion><name sortKey="Chen, Yu" sort="Chen, Yu" uniqKey="Chen Y" first="Yu" last="Chen">Yu Chen</name><name sortKey="Fan, Jinchuan" sort="Fan, Jinchuan" uniqKey="Fan J" first="Jinchuan" last="Fan">Jinchuan Fan</name><name sortKey="Li, Chao" sort="Li, Chao" uniqKey="Li C" first="Chao" last="Li">Chao Li</name><name sortKey="Li, Chunhua" sort="Li, Chunhua" uniqKey="Li C" first="Chunhua" last="Li">Chunhua Li</name><name sortKey="Ma, Hong" sort="Ma, Hong" uniqKey="Ma H" first="Hong" last="Ma">Hong Ma</name><name sortKey="Mi, Kun" sort="Mi, Kun" uniqKey="Mi K" first="Kun" last="Mi">Kun Mi</name><name sortKey="Song, Xicheng" sort="Song, Xicheng" uniqKey="Song X" first="Xicheng" last="Song">Xicheng Song</name><name sortKey="Song, Yufeng" sort="Song, Yufeng" uniqKey="Song Y" first="Yufeng" last="Song">Yufeng Song</name><name sortKey="Tao, Xiaofeng" sort="Tao, Xiaofeng" uniqKey="Tao X" first="Xiaofeng" last="Tao">Xiaofeng Tao</name><name sortKey="Zhang, Bing" sort="Zhang, Bing" uniqKey="Zhang B" first="Bing" last="Zhang">Bing Zhang</name></country><country name="États-Unis"><region name="Texas"><name sortKey="Li, Guojun" sort="Li, Guojun" uniqKey="Li G" first="Guojun" last="Li">Guojun Li</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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