Impact of vascular endothelial growth factor

• Published in: PloS one Vol. 13; no. 5; p. e0197035
• Main Authors: Berardi, Rossana, Torniai, Mariangela, Partelli, Stefano, Rubini, Corrado, Pagliaretta, Silvia, Savini, Agnese, Polenta, Vanessa, Santoni, Matteo, Giampieri, Riccardo, Onorati, Sofia, Barucca, Federica, Murrone, Alberto, Bianchi, Francesca, Falconi, Massimo
• Format: Journal Article
• Language: English
• Published: Public Library of Science 22.05.2018
• Subjects: Chemotherapy; Diagnosis; Genetic aspects; Neuroendocrine tumors; Risk factors; Vascular endothelial growth factor; United States
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0197035

Angiogenesis represents a key event in cancer development, leading to local invasion e metastatization, and might be considered a basic feature in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) with a high expression of angiogenic molecules. We aimed to analyze the prognostic and predictive role of angiogenic factors in GEP-NENs through the analysis of single nucleotide polymorphisms (SNPs) of VEGF-A, VEGFR2 and VEGFR3. The genomic DNA of 58 consecutive patients with GEP-NENs treated at our Institution was extracted from peripheral blood. Two SNPs were identified respectively in VEGF-A (rs2010963G>C, rs699947A>C), VEGFR-2 (rs2305948C>T, rs1870377T>A), and VEGFR-3 (rs307821T>C, rs307826C>A) gene. Gene polymorphisms were determined by Real-Time PCR using TaqMan assays. Median age was 57 years (range 24-79 years); 32 patients were male and 77.5% of NENs were localized in the pancreas. The allele frequency of VEGFR-2 rs2305948T and of VEGF-A rs2010963C showed a trend of higher frequency than in general population (12.1% vs. 8.0% and 34.5% vs. 31.2%, respectively). Three out SNPs (VEGF-A rs699947C, VEGF-A rs2010963GC and VEGFR-3 rs307821C) showed a correlation with an increased risk of disease relapse. Moreover median PFS changes according to the presence of 0-1 SNPs (20.7% of cases; 61.9 months), 2 SNPs (25.9%; 49.2 months) and 3 SNPs (53.4%; 27.8 months) (p = 0.034). Results suggest, for the first time, that specific SNPs in VEGF-A and VEGFR-3 correlate with poor prognosis in GEP-NENs. The identification of this new prognostic factor might be helpful in order to optimize the management of these heterogeneous neoplasms.