Genetic polymorphisms in key hypoxia-regulated downstream molecules and phenotypic correlation in prostate cancer
| Autor: | Ricardo Ribeiro, Carlos Lobato, André Coelho, José Manuel Lopes, José Ramón Vizcaíno, Rui Medeiros, Paulo Príncipe, Helena Coutinho, Avelino Fraga, Carlos Lopes |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A 0301 basic medicine Pathology medicine.medical_specialty Urology Prostatic Hyperplasia Lysyl oxidase Protein-Lysine 6-Oxidase 03 medical and health sciences Prostate cancer 0302 clinical medicine Prostate Carcinoma Humans Medicine Hypoxia-inducible factor 1 Carbonic Anhydrase IX Hypoxia Aged Polymorphism Genetic Tissue microarray Genetic polymorphism business.industry Prostatic Neoplasms General Medicine Middle Aged Hyperplasia Hypoxia-Inducible Factor 1 alpha Subunit medicine.disease Immunohistochemistry Cell Hypoxia Phenotype 030104 developmental biology HIF1A medicine.anatomical_structure Reproductive Medicine 030220 oncology & carcinogenesis Cancer research business Research Article |
| Zdroj: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) Agência para a Sociedade do Conhecimento (UMIC)-FCT-Sociedade da Informação instacron:RCAAP BMC Urology |
| Popis: | 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 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. Electronic supplementary material The online version of this article (doi:10.1186/s12894-017-0201-y) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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