Impact of VEGF, VEGFR, PDGFR, HIF and ERCC1 gene polymorphisms on thymic malignancies outcome after thymectomy

• Published in: Oncotarget Vol. 6; no. 22; pp. 19305 - 19315
• Main Authors: Berardi, Rossana, Brunelli, Alessandro, Pagliaretta, Silvia, Paolucci, Vittorio, Conti, Alessandro, Goteri, Gaia, Refai, Majed, Pompili, Cecilia, Marcantognini, Giulia, Morgese, Francesca, Ballatore, Zelmira, Savini, Agnese, De Lisa, Mariagrazia, Caramanti, Miriam, Santoni, Matteo, Zizzi, Antonio, Piva, Francesco, Mazzanti, Paola, Onofri, Azzurra, Sabbatini, Armando, Scarpelli, Marina, Cascinu, Stefano
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 07.08.2015
• Subjects: Adult; Aged; Aged, 80 and over; Clinical Research Paper; DNA-Binding Proteins - genetics; Endonucleases - genetics; Female; Genotype; Humans; Hypoxia-Inducible Factor 1, alpha Subunit - genetics; Male; Middle Aged; Polymorphism, Single Nucleotide; Prognosis; Receptor, Platelet-Derived Growth Factor alpha - genetics; Thymectomy - methods; Thymoma - genetics; Thymoma - surgery; Thymus Neoplasms - genetics; Thymus Neoplasms - surgery; Treatment Outcome; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor Receptor-2 - genetics; Young Adult; tumor risk; single nucleotide polymorphism; prognosis; angiogenesis; thymic epithelial tumor
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.4191

We aimed to analyze genotypes of VEGF-A, VEGFR2, Flt4, PDGFRα, HIF-1α and ERCC1 and their correlation with thymic tumor risk and patient outcome. DNA of 57 consecutive patients (43 thymomas and 14 thymic carcinomas) who underwent total thymectomy at our Institution was extracted from paraffin-embedded tissue. We selected polymorphisms in the following genes:HIF1-α (rs2057482T > C, rs1951795A > C, rs2301113C > A, rs10873142C > T, rs11158358G > C, rs12434438G > A, rs11549465C > T, rs11549467G > A), VEGF-A (rs2010963G > C, rs699947A > C), VEGFR-2 (rs2305948C > T, rs1870377T > A), VEGFR-3 (rs307826T > C, rs307821C > A), PDGFR-α (rs35597368C > T) and ERCC1 (rs11615A > G). Gene polymorphisms were determined by Real-Time PCR using TaqMan assays. As compared to the general population, the allele frequency of PDGFR-α rs35597368T was significantly higher (95% vs. 87%, p = 0.036), while the frequency of alleles HIF1-α rs2057482C (78% vs. 90%), rs1951795C (69% vs. 87%), rs2301113A (70% vs. 83%), rs10873142T (70% vs. 87%), rs11158358C (75% vs. 88%), rs12434438A (67% vs. 84%) were significantly lower. VEGFR-3 rs307821C frequency was significantly higher in thymomas vs. thymic carcinomas (79% vs. 72%, p = 0.0371). The following factors were significantly correlated with a longer overall survival: VEGFR-3 rs307826C, VEGFR-2 rs1870377A, PDGFR-α rs35597368T/C, HIF1-α rs2301113C, rs2057482C/T, rs1951795C, rs11158358G/C and rs10873142T/C, ERCC1 rs11615A (p < 0.05). Our results suggest, for the first time, that PDGFR-α, HIF-1α and VEGFR-3 SNPs are associated with thymic cancer risk and survival.