Profiling of Vascular Endothelial Growth Factor Receptor Heterogeneity Identifies Protein Expression-defined Subclasses of Human Non-small Cell Lung Carcinoma
Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved..
BACKGROUND: the vascular endothelial growth factor (VEGF) pathway plays a prominent role in the growth and progression of human cancer, including non-small cell lung carcinoma (NSCLC). The key mediators of VEGF signaling are a family of related receptor tyrosine kinases that include VEGFR1, VEGFR2, and VEGFR3. The relative expression levels, activity, and cross-talk among these receptors may contribute to response of NSCLC to anti-angiogenic therapies, and a better systematic, translatable approach to categorizing tumors is needed.
MATERIALS AND METHODS: We comparatively evaluated immunohistochemical expression of the three VEGFRs in archival primary NSCLC tissues (n=96).
RESULTS: VEGFR1 and VEGFR2 were localized both in vessels and tumor cells, while VEGFR3 was only localized in tumor vessels. A set of eight VEGFR staining subclasses were identified: Triple VEGFR positive (n=11, 11.5%), VEGFR1 predominant (n=22, 22.9%), VEGFR2 predominant (n=9, 9.4%), VEGFR3 predominant (n=3, 3.1%), VEGFR1/2 predominant (13, 13.5%), VEGFR1/3 predominant (2, 2.1%), VEGFR2/3 predominant (n=8, 8.3%), and triple VEGFR negative (n=28, 29.2%). An objective categorization based on K-means clustering revealed four clusters, three of which showed high VEGFR2 compared to VEGFR3 (30.7% of cases), cases high in both VEGFR2 and VEGFR3 (18.2%), and cases that were negative/low for both VEGFR2 and VEGFR3 (45.4%). A positive association between VEGFR2 and VEGFR3 was found, however no associations were observed between VEGFR1 and VEGFR2, nor VEGFR1 and VEGFR3.
CONCLUSION: The proposed subclasses of NSCLC are an approach for complementing lines of investigation of anti-angiogenic therapies beginning with systematic characterization of the disease.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2016 |
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| Erschienen: |
2016 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:36 |
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| Enthalten in: |
Anticancer research - 36(2016), 7 vom: 01. Juli, Seite 3277-88 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Holzer, Timothy R [VerfasserIn] |
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| Anmerkungen: |
Date Completed 06.01.2017 Date Revised 07.01.2017 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Profiling of Vascular Endothelial Growth Factor Receptor Heterogeneity Identifies Protein Expression-defined Subclasses of Human Non-small Cell Lung Carcinoma |
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| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved. | ||
| 520 | |a BACKGROUND: the vascular endothelial growth factor (VEGF) pathway plays a prominent role in the growth and progression of human cancer, including non-small cell lung carcinoma (NSCLC). The key mediators of VEGF signaling are a family of related receptor tyrosine kinases that include VEGFR1, VEGFR2, and VEGFR3. The relative expression levels, activity, and cross-talk among these receptors may contribute to response of NSCLC to anti-angiogenic therapies, and a better systematic, translatable approach to categorizing tumors is needed | ||
| 520 | |a MATERIALS AND METHODS: We comparatively evaluated immunohistochemical expression of the three VEGFRs in archival primary NSCLC tissues (n=96) | ||
| 520 | |a RESULTS: VEGFR1 and VEGFR2 were localized both in vessels and tumor cells, while VEGFR3 was only localized in tumor vessels. A set of eight VEGFR staining subclasses were identified: Triple VEGFR positive (n=11, 11.5%), VEGFR1 predominant (n=22, 22.9%), VEGFR2 predominant (n=9, 9.4%), VEGFR3 predominant (n=3, 3.1%), VEGFR1/2 predominant (13, 13.5%), VEGFR1/3 predominant (2, 2.1%), VEGFR2/3 predominant (n=8, 8.3%), and triple VEGFR negative (n=28, 29.2%). An objective categorization based on K-means clustering revealed four clusters, three of which showed high VEGFR2 compared to VEGFR3 (30.7% of cases), cases high in both VEGFR2 and VEGFR3 (18.2%), and cases that were negative/low for both VEGFR2 and VEGFR3 (45.4%). A positive association between VEGFR2 and VEGFR3 was found, however no associations were observed between VEGFR1 and VEGFR2, nor VEGFR1 and VEGFR3 | ||
| 520 | |a CONCLUSION: The proposed subclasses of NSCLC are an approach for complementing lines of investigation of anti-angiogenic therapies beginning with systematic characterization of the disease | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Fulford, Angie D |e verfasserin |4 aut | |
| 700 | 1 | |a Reising, Leslie O'Neill |e verfasserin |4 aut | |
| 700 | 1 | |a Nedderman, Drew M |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xuekui |e verfasserin |4 aut | |
| 700 | 1 | |a Benjamin, Laura E |e verfasserin |4 aut | |
| 700 | 1 | |a Schade, Andrew E |e verfasserin |4 aut | |
| 700 | 1 | |a Nasir, Aejaz |e verfasserin |4 aut | |
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