No abstract

Several mutations act as driver mutations in breast cancer, including GATA3 mutations. Reports of the relation between GATA3 mutations and breast cancer prognosis remain conflicting. Also, the role of GATA3 germline mutations is not well studied. We hypothesize that different mutation types could have different effects. Also, this study aims to assess effect of GATA3 mutations on GATA3 protein function as a transcription factor, and target pathways affected. DNA from de novo breast cancer female patients was sequenced to detect exon 6 GATA3 mutation. Sequence analysis was performed along with clinical and prognostic parameters and disease-free survival. Public datasets were analyzed for differentially expressed genes and pathways with mutant GATA3 patients. Mutations in GATA3 exon 6 were detected in 56.1% of patients (including 2 novel, Lys368fs, Pro354Lys). Intronic mutations were significantly higher in long disease-free survival group, while frameshift mutations were significantly higher in short DFS group. Patients with tumor size ≥20 had significantly higher protein coding and lower intronic mutations compared to patients with tumor size <20 mm. Differential expression and pathway analysis showed that mutant GATA3 had lost its negative regulatory effect on several pathways such as: signaling by interleukins, regulation of TP53 expression, and RUNX3 regulated CDKN1A transcription pathway. PIK3CA, SKP1, FBP1, SMAD3, ANXA9 and CLSTN2 were positively correlated to wild-type GATA3 expression, but not mutant GATA3. Intronic germline mutations of GATA3 could be related to better prognosis, while protein coding GATA3 germline mutations could be related to unfavorable prognosis. GATA3 mutations lead to dysregulation of pathways related to immunity, breast cancer development, and metabolism. Impact statement GATA3 mutations are known to play an important role in breast cancer progression. The exact role and mechanisms of these mutations remain controversial as some studies suggest a relation to breast tumor growth, while others suggest a relation to longer survival. GATA3 germline mutations are not well studied in breast cancer. In this study, it was hypothesized that different types of GATA3 mutations could contribute to the breast cancer progression in different ways. GATA3 exon 6, which is important for GATA3 protein functions, was reported to have hotspots, and hence it was selected for study. Intronic GATA3 germline mutations were found to be related to favorable prognosis, while protein coding mutations were found to be related to unfavorable prognosis. Bioinformatics study of large publically available datasets showed that GATA3 mutations lead to dysregulation of pathways related to T-cells activation, inflammation, and breast cancer development.

Background: Neopterin is a proinflammatorymarker which participates in cell-mediated immunity, and its elevated concentrations declare the presence of interferon-γ in body fluids. In thisstudy, neopterin concentrations were determined in patients with chronic hepatitis C virus (HCV)to assess whether its plasma level can be used to predict the response to antiviral therapy by pegIFNγ combined with ribavirin before starting the treatment. Materials and Mehtods: A total of 54 subjects (all males with an average age of 46.12± 9.89) were included in this study. Neopterin levels were evaluatedby Enzyme-linked immunosorbent assay (ELIZA) in HCV patients treated with peylated interferon combined with ribavirin. Liver function tests (Aspartate aminotransferase, Alanine aminotransferase), albumin and creatinine concentrations were also estimatied. Results: Mean and median pretreatment neopterin levelsshowed no statistically difference between patients with sustained virological response (cured)and non-responders (relapsed) where the concentrations in both groups were≥16 nmol/L.On the other hand, a positive correlation was observed between neopterin level and creatinine at (p ≤ 0.05). Conclusion: Our study suggests that the pretreatment level of neopterin might not be used in routine clinical practice as a marker to predict the response to antiviral therapy in HCVpatients.

Back ground Chronic hepatitis C (CHC) virus infection is a major cause of chronic liver disease and death throughout the world; several studies have shown an impaired health-related quality of life (HRQoL)in patients with CHC compared to general population whereas treatment of this disease often produce varying degrees of adverse effects which may negatively affect a patient’s HRQoL. Aim To measure the change in the HRQoL of the patients after the treatment and compare this change with response to treatment. Methodology 427 chronic HCV newly recruited patients to receive pegylated interferon and ribavirin for 48 weeks in the National Hepatology & Tropical medicine Research Institute were selected and completed the SF-36 quality of life questionnaire before treatment and at the end of treatment then followed up for another six months to determine sustained virological response (SVR). Results Patients’ HRQoL showed deterioration in all domains at the end of treatment compared to baseline measures with high statistical significant differences (p &lt; 0.001). Non-responders showed more deterioration than patients with SVR especially in the perception of “mental health, social wellbeing, bodily pain, and general health”. Conclusion Sustained virological response rate between chronic hepatitis C patients receiving combined anti-viral therapy (interferon and ribavirin) was 63.5%. HRQoL of patients receiving combined anti-viral therapy (interferon and ribavirin) deteriorated during the course of treatment till the end of treatment. Patients with SVR were less deteriorated than non-responders.