Publication
Genetic polymorphisms in key hypoxia-regulated downstream molecules and phenotypic correlation in prostate cancer
| dc.contributor.author | Fraga, A. | |
| dc.contributor.author | Ribeiro, R. | |
| dc.contributor.author | Coelho, A. | |
| dc.contributor.author | Vizcaíno, J. | |
| dc.contributor.author | Coutinho, H. | |
| dc.contributor.author | Lopes, J. | |
| dc.contributor.author | Príncipe, P. | |
| dc.contributor.author | Lobato, C. | |
| dc.contributor.author | Lopes, C. | |
| dc.contributor.author | Medeiros, R. | |
| dc.date.accessioned | 2017-08-29T11:53:51Z | |
| dc.date.available | 2017-08-29T11:53:51Z | |
| dc.date.issued | 2017-01-31 | |
| dc.description.abstract | Background In this study we sought if, in their quest to handle hypoxia, prostate tumors express target hypoxia-associated molecules and their correlation with putative functional genetic polymorphisms. Methods Representative areas of prostate carcinoma (n = 51) and of nodular prostate hyperplasia (n = 20) were analysed for hypoxia-inducible factor 1 alpha (HIF-1α), carbonic anhydrase IX (CAIX), lysyl oxidase (LOX) and vascular endothelial growth factor (VEGFR2) immunohistochemistry expression using a tissue microarray. DNA was isolated from peripheral blood and used to genotype functional polymorphisms at the corresponding genes (HIF1A +1772 C > T, rs11549465; CA9 + 201 A > G; rs2071676; LOX +473 G > A, rs1800449; KDR – 604 T > C, rs2071559). Results Immunohistochemistry analyses disclosed predominance of positive CAIX and VEGFR2 expression in epithelial cells of prostate carcinomas compared to nodular prostate hyperplasia (P = 0.043 and P = 0.035, respectively). In addition, the VEGFR2 expression score in prostate epithelial cells was higher in organ-confined and extra prostatic carcinoma compared to nodular prostate hyperplasia (P = 0.031 and P = 0.004, respectively). Notably, for LOX protein the immunoreactivity score was significantly higher in organ-confined carcinomas compared to nodular prostate hyperplasia (P = 0.015). The genotype-phenotype analyses showed higher LOX staining intensity for carriers of the homozygous LOX +473 G-allele (P = 0.011). Still, carriers of the KDR−604 T-allele were more prone to have higher VEGFR2 expression in prostate epithelial cells (P < 0.006). Conclusions Protein expression of hypoxia markers (VEGFR2, CAIX and LOX) on prostate epithelial cells was different between malignant and benign prostate disease. Two genetic polymorphisms (LOX +473 G > A and KDR−604 T > C) were correlated with protein level, accounting for a potential gene-environment effect in the activation of hypoxia-driven pathways in prostate carcinoma. Further research in larger series is warranted to validate present findings. | pt_PT |
| dc.description.version | info:eu-repo/semantics/publishedVersion | pt_PT |
| dc.identifier.citation | BMC Urol. 2017 Jan 31;17(1):12 | pt_PT |
| dc.identifier.doi | 10.1186/s12894-017-0201-y | pt_PT |
| dc.identifier.issn | 1471-2490 | |
| dc.identifier.uri | http://hdl.handle.net/10400.16/2170 | |
| dc.language.iso | eng | pt_PT |
| dc.peerreviewed | yes | pt_PT |
| dc.publisher | BioMed Central | pt_PT |
| dc.relation.publisherversion | https://bmcurol.biomedcentral.com/articles/10.1186/s12894-017-0201-y | pt_PT |
| dc.subject | Genetic polymorphism | pt_PT |
| dc.subject | Hypoxia | pt_PT |
| dc.subject | Hypoxia-inducible factor 1 | pt_PT |
| dc.subject | Prostate cancer | pt_PT |
| dc.title | Genetic polymorphisms in key hypoxia-regulated downstream molecules and phenotypic correlation in prostate cancer | pt_PT |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.citation.conferencePlace | England | pt_PT |
| oaire.citation.issue | 1 | pt_PT |
| oaire.citation.startPage | 12 | pt_PT |
| oaire.citation.title | BMC Urology | pt_PT |
| oaire.citation.volume | 17 | pt_PT |
| rcaap.rights | openAccess | pt_PT |
| rcaap.type | article | pt_PT |