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P04.11GENETIC POLYMORPHISMS OF EGF 5'-UTR IN PATIENTS WITH GLIOMA: A POSSIBLE PREDICTIVE MARKER OF OUTCOME

ABSTRACT: BACKGROUND: Epidermal growth factor (EGF) plays an important role in carcinogenesis. An adenine (A) to guanine (G) single nucleotide polymorphism at position 61 in the 5'-untranslated region (5'-UTR) of the EGF gene has been found to be associated with levels of EGF production and contribute to the risk of glioma. However, published data are contradictory. EGF +61G/A polymorphism may contribute to the risk of glioma in different ethnic group. Patients with glioma and GG genotype have been reported to have a risk of poorer outcome than patients with AA genotype. Purpose of this study is to investigate the potential role of this polymorphism in cancer progression and its role as predictive marker of outcome in glioma caucasian patients. METHODS: The significant SNP rs4444903, EGF 61A/G, was analyzed in glioma patients and was determined by means of Polymerase Chain Reaction and Direct Sequencing method from blood samples. Association of this genetic polymorphism with clinical and pathological data of patients was evaluated. RESULTS: We investigated EGF +61G/A polymorphism in 28 glioma patients. EGF +61G allele has been found in 68% of glioma patients (22% G/G genotype and 46% A/G genotype). In astrocytomas, EGF +61G allele represents a 83% frequency; in glioblastomas and in oligodendrogliomas, EGF +61G allele frequency represents respectively 73% and 54%. In WHO IV gliomas, the EGF +61G allele represents a 72% frequency, (27% G/G and 45% A/G ), in WHO III gliomas a 81% frequency (54% G/G and 27% A/G ) and in WHO II gliomas a 33% frequency (80% A/G ). Median PFS of glioblastoma patients was 9 months. 79% of glioblastoma patients with a relapsing disease showed the G/G and A/G genotype. No difference was detected in the others histotypes. CONCLUSIONS: Our data confirm previous studies which reported G allele as a risk factor for glioma in Caucasian. G/A and G/G genotypes seem to be more rappresentative in high grade gliomas . Despite limited number of patients, our study supports the predictive role of EGF 61 A/G polymorphism in GBM. Additional large studies are warranted to confirm the role of EGF polymorphism as indipendent prognostic factor in glioma.

SUBMITTER: Dealis C

PROVIDER: S-EPMC4185487 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Project description:In vitro fertilization (IVF) is an effective means to treat infertility, but the pregnancy rate is still unsatisfactory and reliable markers to predict pregnancy outcome are ill-defined. Myeloid-derived suppressor cell (MDSC) are critically involved in decisions related to the acceptance or rejection of foreign fetal antigens by the maternal immune system. However, factors that regulate peripheral blood MDSC during pre-pregnancy are poorly defined. Thus, the goal of this study was to assess the relationships among serum estradiol (E2) and endothelial growth factor (VEGF) levels, MDSC ratios, and pregnancy outcome associated with IVF. Patients undergoing IVF treatment (n = 54) were recruited from January to June 2018. Levels of E2 and VEGF were measured by ELISA, MDSC ratios among peripheral blood mononuclear cells (PBMC) were detected by flow cytometry, and the crosstalk among these parameters was analyzed. A receiver operating characteristic curve (ROC) of MDSC levels was plotted to assess this measure as an independent predictive factor for pregnancy. In addition, we analyzed the possible involvement of molecular pathways by bioinformatics. When E2 levels were <4,000 pg/ml, MDSC proportion was positively correlated with serum E2 and VEGF levels. However, when E2 levels were >4,000 pg/ml, MDSC ratio and VEGF levels were negatively correlated with E2. A ROC curve revealed that the percentage of MDSC had better sensitivity and specificity at a concentration of 8.22% (0.875 and 0.75, respectively; area under the curve (AUC) = 0.859) to predict pregnancy success, based on multiple logistic regression analysis. Furthermore, we found 12 target genes of E2 and VEGF, and also functional genes related to MDSC, indicating potential protein-protein interactions underlying these associations. In summary, we showed that E2, depending on its concentration, might play a dichotomous role in influencing the MDSC proportion by regulating VEGF. In IVF patients, an increased MDSC ratio among PBMC was highly correlated with elevated pregnancy rates, independent of the effects of E2, which might provide new insight into immune-related miscarriage and IVF failure.

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P04.11GENETIC POLYMORPHISMS OF EGF 5'-UTR IN PATIENTS WITH GLIOMA: A POSSIBLE PREDICTIVE MARKER OF OUTCOME

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