Expression and prognostic significance of vascular endothelial growth factor-A (VEGF-A) and its receptor in canine prostate cancer
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1002/pros.24199 http://hdl.handle.net/11449/229218 |
Resumo: | Background: Vascular endothelial growth factor-A (VEGF-A) and its receptor, VEGF receptor-2 (VEGFR-2), represent a complex family of angiogenic molecules consisting of different ligands and receptors. Due to the importance of VEGF-A/VEGFR-2 signaling in tumor proliferation and angiogenesis, this study aimed to evaluate the protein and gene expression levels of VEGF-A and VEGFR-2 in canine prostate cancer (PC). Methods: We analyzed VEGF-A and VEGFR-2 expression in 87 PC samples by immunohistochemistry and quantitative-polymerase chain reaction. PC samples were graded according to the Gleason score and the immunohistochemical staining for VEGF-A and VEGFR-2 was quantified using a selected threshold from the ImageJ Software. Microvascular density was assessed by cluster of differentiation 31 staining and counting the number of positive vessels. Additionally, the homology of VEGF-A and VEGFR-2 between humans and dogs was assessed, followed by the construction of a protein structure homology model to compare the tertiary structures of these proteins in both species. Results: Negative to weakly positive expression levels of VEGF-A and VEGFR-2 were observed in the epithelial cells of the normal prostate (NP) and prostatic hyperplasia samples. In contrast, the canine proliferative atrophy and PC samples exhibited higher VEGF-A (p <.0001) and VEGFR-2 (p <.0001) compared to NP. Moreover, positive correlations between the expression levels of VEGF-A and VEGFR-2 (Spearman's coefficient (r) =.68, p =.013) and the expression levels of VEGF-A and VEGFR-2 proteins (r =.8, p <.0001) were also observed in the NP samples. Additionally, the patients with PC exhibiting higher VEGFR-2 expression levels experienced a shorter survival period (p =.0372). Furthermore, we found an association between the microvascular density and overall survival. Dogs with a higher number of vessels showed a shorter survival time. We further demonstrated that the VEGF-A and VEGFR-2 exhibited high homology between humans and dogs, and identified their protein structures in both species. Conclusions: In conclusion, VEGFR-2 appears to be an independent prognostic factor in animals with PC. VEGF-A and VEGFR-2 are highly conserved between humans and dogs, which can be investigated further in future cross-species studies to explore their therapeutic applications. |
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Expression and prognostic significance of vascular endothelial growth factor-A (VEGF-A) and its receptor in canine prostate cancerangiogenesiscancerdogVEGF-AVEGFR-2Background: Vascular endothelial growth factor-A (VEGF-A) and its receptor, VEGF receptor-2 (VEGFR-2), represent a complex family of angiogenic molecules consisting of different ligands and receptors. Due to the importance of VEGF-A/VEGFR-2 signaling in tumor proliferation and angiogenesis, this study aimed to evaluate the protein and gene expression levels of VEGF-A and VEGFR-2 in canine prostate cancer (PC). Methods: We analyzed VEGF-A and VEGFR-2 expression in 87 PC samples by immunohistochemistry and quantitative-polymerase chain reaction. PC samples were graded according to the Gleason score and the immunohistochemical staining for VEGF-A and VEGFR-2 was quantified using a selected threshold from the ImageJ Software. Microvascular density was assessed by cluster of differentiation 31 staining and counting the number of positive vessels. Additionally, the homology of VEGF-A and VEGFR-2 between humans and dogs was assessed, followed by the construction of a protein structure homology model to compare the tertiary structures of these proteins in both species. Results: Negative to weakly positive expression levels of VEGF-A and VEGFR-2 were observed in the epithelial cells of the normal prostate (NP) and prostatic hyperplasia samples. In contrast, the canine proliferative atrophy and PC samples exhibited higher VEGF-A (p <.0001) and VEGFR-2 (p <.0001) compared to NP. Moreover, positive correlations between the expression levels of VEGF-A and VEGFR-2 (Spearman's coefficient (r) =.68, p =.013) and the expression levels of VEGF-A and VEGFR-2 proteins (r =.8, p <.0001) were also observed in the NP samples. Additionally, the patients with PC exhibiting higher VEGFR-2 expression levels experienced a shorter survival period (p =.0372). Furthermore, we found an association between the microvascular density and overall survival. Dogs with a higher number of vessels showed a shorter survival time. We further demonstrated that the VEGF-A and VEGFR-2 exhibited high homology between humans and dogs, and identified their protein structures in both species. Conclusions: In conclusion, VEGFR-2 appears to be an independent prognostic factor in animals with PC. VEGF-A and VEGFR-2 are highly conserved between humans and dogs, which can be investigated further in future cross-species studies to explore their therapeutic applications.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Department of Veterinary Surgery and Anesthesiology School of Veterinary Medicine and Animal Science São Paulo State University—UNESPDepartment of Veterinary Clinic School of Veterinary Medicine and Animal Science São Paulo State University—UNESPSchool of Veterinary Science The University of Queensland Gatton CampusInstitute of Health Sciences Paulista University—UNIPDepartment of Veterinary Surgery and Anesthesiology School of Veterinary Medicine and Animal Science São Paulo State University—UNESPDepartment of Veterinary Clinic School of Veterinary Medicine and Animal Science São Paulo State University—UNESPFAPESP: 2015/25400-7Universidade Estadual Paulista (UNESP)The University of Queensland Gatton CampusPaulista University—UNIPLeis-Filho, Antonio Fernando [UNESP]Lainetti, Patricia deFaria [UNESP]Kobayashi, Priscila Emiko [UNESP]Palmieri, ChiaraAmorim, Renée Laufer [UNESP]Fonseca-Alves, Carlos Eduardo [UNESP]2022-04-29T08:31:17Z2022-04-29T08:31:17Z2021-10-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article1021-1031http://dx.doi.org/10.1002/pros.24199Prostate, v. 81, n. 14, p. 1021-1031, 2021.1097-00450270-4137http://hdl.handle.net/11449/22921810.1002/pros.241992-s2.0-85111376526Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengProstateinfo:eu-repo/semantics/openAccess2022-04-29T08:31:17Zoai:repositorio.unesp.br:11449/229218Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T21:52:54.656824Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Expression and prognostic significance of vascular endothelial growth factor-A (VEGF-A) and its receptor in canine prostate cancer |
title |
Expression and prognostic significance of vascular endothelial growth factor-A (VEGF-A) and its receptor in canine prostate cancer |
spellingShingle |
Expression and prognostic significance of vascular endothelial growth factor-A (VEGF-A) and its receptor in canine prostate cancer Leis-Filho, Antonio Fernando [UNESP] angiogenesis cancer dog VEGF-A VEGFR-2 |
title_short |
Expression and prognostic significance of vascular endothelial growth factor-A (VEGF-A) and its receptor in canine prostate cancer |
title_full |
Expression and prognostic significance of vascular endothelial growth factor-A (VEGF-A) and its receptor in canine prostate cancer |
title_fullStr |
Expression and prognostic significance of vascular endothelial growth factor-A (VEGF-A) and its receptor in canine prostate cancer |
title_full_unstemmed |
Expression and prognostic significance of vascular endothelial growth factor-A (VEGF-A) and its receptor in canine prostate cancer |
title_sort |
Expression and prognostic significance of vascular endothelial growth factor-A (VEGF-A) and its receptor in canine prostate cancer |
author |
Leis-Filho, Antonio Fernando [UNESP] |
author_facet |
Leis-Filho, Antonio Fernando [UNESP] Lainetti, Patricia deFaria [UNESP] Kobayashi, Priscila Emiko [UNESP] Palmieri, Chiara Amorim, Renée Laufer [UNESP] Fonseca-Alves, Carlos Eduardo [UNESP] |
author_role |
author |
author2 |
Lainetti, Patricia deFaria [UNESP] Kobayashi, Priscila Emiko [UNESP] Palmieri, Chiara Amorim, Renée Laufer [UNESP] Fonseca-Alves, Carlos Eduardo [UNESP] |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (UNESP) The University of Queensland Gatton Campus Paulista University—UNIP |
dc.contributor.author.fl_str_mv |
Leis-Filho, Antonio Fernando [UNESP] Lainetti, Patricia deFaria [UNESP] Kobayashi, Priscila Emiko [UNESP] Palmieri, Chiara Amorim, Renée Laufer [UNESP] Fonseca-Alves, Carlos Eduardo [UNESP] |
dc.subject.por.fl_str_mv |
angiogenesis cancer dog VEGF-A VEGFR-2 |
topic |
angiogenesis cancer dog VEGF-A VEGFR-2 |
description |
Background: Vascular endothelial growth factor-A (VEGF-A) and its receptor, VEGF receptor-2 (VEGFR-2), represent a complex family of angiogenic molecules consisting of different ligands and receptors. Due to the importance of VEGF-A/VEGFR-2 signaling in tumor proliferation and angiogenesis, this study aimed to evaluate the protein and gene expression levels of VEGF-A and VEGFR-2 in canine prostate cancer (PC). Methods: We analyzed VEGF-A and VEGFR-2 expression in 87 PC samples by immunohistochemistry and quantitative-polymerase chain reaction. PC samples were graded according to the Gleason score and the immunohistochemical staining for VEGF-A and VEGFR-2 was quantified using a selected threshold from the ImageJ Software. Microvascular density was assessed by cluster of differentiation 31 staining and counting the number of positive vessels. Additionally, the homology of VEGF-A and VEGFR-2 between humans and dogs was assessed, followed by the construction of a protein structure homology model to compare the tertiary structures of these proteins in both species. Results: Negative to weakly positive expression levels of VEGF-A and VEGFR-2 were observed in the epithelial cells of the normal prostate (NP) and prostatic hyperplasia samples. In contrast, the canine proliferative atrophy and PC samples exhibited higher VEGF-A (p <.0001) and VEGFR-2 (p <.0001) compared to NP. Moreover, positive correlations between the expression levels of VEGF-A and VEGFR-2 (Spearman's coefficient (r) =.68, p =.013) and the expression levels of VEGF-A and VEGFR-2 proteins (r =.8, p <.0001) were also observed in the NP samples. Additionally, the patients with PC exhibiting higher VEGFR-2 expression levels experienced a shorter survival period (p =.0372). Furthermore, we found an association between the microvascular density and overall survival. Dogs with a higher number of vessels showed a shorter survival time. We further demonstrated that the VEGF-A and VEGFR-2 exhibited high homology between humans and dogs, and identified their protein structures in both species. Conclusions: In conclusion, VEGFR-2 appears to be an independent prognostic factor in animals with PC. VEGF-A and VEGFR-2 are highly conserved between humans and dogs, which can be investigated further in future cross-species studies to explore their therapeutic applications. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-10-01 2022-04-29T08:31:17Z 2022-04-29T08:31:17Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1002/pros.24199 Prostate, v. 81, n. 14, p. 1021-1031, 2021. 1097-0045 0270-4137 http://hdl.handle.net/11449/229218 10.1002/pros.24199 2-s2.0-85111376526 |
url |
http://dx.doi.org/10.1002/pros.24199 http://hdl.handle.net/11449/229218 |
identifier_str_mv |
Prostate, v. 81, n. 14, p. 1021-1031, 2021. 1097-0045 0270-4137 10.1002/pros.24199 2-s2.0-85111376526 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Prostate |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
1021-1031 |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
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1808129369583910912 |