Expression of Angiogenesis-related Genes in a Group of Iranian Cases of Breast Cancer

Abstract

This study aims to design an angiogenesis gene expression profile; to study angiogenesis gene expression profile in breast cancer; and to map angiogenesis gene expression profile in individual participants. In molecular etiology of each disease, there are some important molecules involved in the related pathways. From the viewpoint of precision medicine, molecular etiology of a disease is different person by person because of genetic variations of the genes involved in these pathways. This point of view intends researchers of drug development to design novel drugs for targeted therapy based on the exact etiology. In the case of angiogenesis, there is a drug profile parallel to the molecular profile. Bevacizumab, sunitinib and aflibercept are examples of anti-angiogenic drugs. A hallmark of solid tumors is sustained angiogenesis. Vascular endothelial growth factors (VEGF), VEGF receptors (VEGFR) and placental growth factor (PlGF) are involved in angiogenesis. We aimed to study the gene expression profile of angiogenesis including VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGFR-1, VEGFR-2, VEGFR-3 and PlGF in an Iranian group of patients undergoing breast surgery due to breast cancer and breast fibroadenoma. Tumor tissue samples of a group of patients with invasive ductal carcinoma (IDC) and a group of patients with fibroadenoma (Fib) were used. Gene expression was studied by real-time quantitative polymerase chain reaction (q-PCR) and fold changes (FC) with their 95% confidence intervals (CI) were reported based on calibration with normal breast tissue. All the genes showed significant up-regulation in IDC group. The extensive up-regulation was for VEGFR-2 (FC=52.68; 95% CI=17.96-154.47; P<0.001). In Fib group, PlGF showed a significant upregulation (FC=10.41; 95% CI=5.35-20.26; P=0.002). Comparison of IDC group with Fib group showed significant up-regulation of VEGFR-1, VEGFR-2 and VEGFR-3 in IDC group (P<0.05). Malignancy of breast tumors is associated with overexpression of all the genes of this profile. However, only VEGFRs showed up-regulation in comparison to benign tumors. Individualized targeted therapy, according to this profile, should be studied in the future.