Genetic polymorphisms in key hypoxia-regulated downstream molecules and phenotypic correlation in prostate cancer

• Type: Article in International Scientific Journal
• Date: 2017

Authors

Fraga, A (Author) Other; Ribeiro, R (Author) Other; Coelho, A (Author) Other; Vizcaino, JR (Author) Other; Coutinho, H (Author) Other; Lopes, JM (Author) FMUP; Principe, P (Author) Other; Lobato, C (Author) Other; Lopes, C (Author) Other; Rui Medeiros (Author) ICBAS

Journal

Title: BMC Urology

Vol. 17

Pages: 1-12

ISSN: 1471-2490

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 26 Citations

Scopus - 26 Citations

Other information

Authenticus ID: P-00M-HE1

DOI: 10.1186/s12894-017-0201-y

Abstract (EN): 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-1a), 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 Tallele 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12