BECN1 mRNA expression in breast cancer tissue; significant correlation to tumor grade.

Breast cancer (BC) is a heterogenous disease with multiple pathways implicated in its development, progression, and drug resistance. Autophagy, a cellular process responsible for self-digestion of damaged organelles, had been recognized as eminent player in cancer progression and chemotherapeutic resistance. The haploinsufficiency of Beclin 1 (BECN1), autophagy protein, is believed to contribute to cancer pathogenesis and progression. In our study, we investigated the expression of BECN1 in a BC female Egyptian patient cohort, as well as its prognostic role through evaluating its association with disease free survival (DFS) after 2 years follow up and association of tumor clinicopathological features. Twenty frozen female BC tissue samples and 17 adjacent normal tissue were included and examined for the expression levels of BECN1. Although the tumor tissues showed lower expression 0.73 (0-8.95) than their corresponding normal tissues 1.02 (0.04-19.59), it was not statistically significant, p: 0.463. BECN1 expression was not associated with stage, nodal metastasis or tumor size, p:0.435, 0.541, 0.296, respectively. However, statistically significant negative correlation was found between grade and BECN1 mRNA expression in the studied cases, p:0.028. BECN1 expression had no statistically significant association with DFS, P = 0.944. However, we observed that triple negative (TNBC) cases had significantly lower DFS rate than luminal BC patients, p: 0.022, with mean DFS 19.0 months, while luminal BC patients had mean DFS of 23.41 months. Our study highlights the potential role of BECN1 in BC pathogenesis, showing that BECN1 expression correlates with poorer differentiation of BC, indicating its probable link with disease aggressiveness. DFS two years follow up showed that TNBC subtype remains associated with less favorable prognosis.

Genomics in Egypt: Current Status and Future Aspects.

Egypt is the third most densely inhabited African country. Due to the economic burden and healthcare costs of overpopulation, genomic and genetic testing is a huge challenge. However, in the era of precision medicine, Egypt is taking a shift in approach from "one-size-fits all" to more personalized healthcare via advancing the practice of medical genetics and genomics across the country. This shift necessitates concrete knowledge of the Egyptian genome and related diseases to direct effective preventive, diagnostic and counseling services of prevalent genetic diseases in Egypt. Understanding disease molecular mechanisms will enhance the capacity for personalized interventions. From this perspective, we highlight research efforts and available services for rare genetic diseases, communicable diseases including the coronavirus 2019 disease (COVID19), and cancer. The current state of genetic services in Egypt including availability and access to genetic services is described. Drivers for applying genomics in Egypt are illustrated with a SWOT analysis of the current genetic/genomic services. Barriers to genetic service development in Egypt, whether economic, geographic, cultural or educational are discussed as well. The sensitive topic of communicating genomic results and its ethical considerations is also tackled. To understand disease pathogenesis, much can be gained through the advancement and integration of genomic technologies via clinical applications and research efforts in Egypt. Three main pillars of multidisciplinary collaboration for advancing genomics in Egypt are envisaged: resources, infrastructure and training. Finally, we highlight the recent national plan to establish a genome center that will aim to prepare a map of the Egyptian human genome to discover and accurately determine the genetic characteristics of various diseases. The Reference Genome Project for Egyptians and Ancient Egyptians will initialize a new genomics era in Egypt. We propose a multidisciplinary governance system in Egypt to support genomic medicine research efforts and integrate into the healthcare system whilst ensuring ethical conduct of data.

Establishment of reference intervals of clinical chemistry analytes for the adult population in Egypt.

BACKGROUND: This is the first Egyptian nationwide study for derivation of reference intervals (RIs) for 34 major chemistry analytes. It was conducted as a part of the global initiative by the IFCC Committee on Reference Intervals and Decision Limits (C-RIDL) for establishing country-specific RIs based on a harmonized protocol. METHODS: 691 apparently healthy volunteers aged ≥18 years were recruited from multiple regions in Egypt. Serum specimens were analyzed in two centers. The harmonization and standardization of test results were achieved by measuring value-assigned serum panel provided by C-RIDL. The RIs were calculated by parametric method. Sources of variation of reference values (RVs) were evaluated by multiple regression analysis. The need for partitioning by sex, age, and region was judged primarily by standard deviation ratio (SDR). RESULTS: Gender-specific RIs were required for six analytes including total bilirubin (TBil), aspartate and alanine aminotransferase (AST, ALT). Seven analytes required age-partitioning including glucose and low-density lipoprotein cholesterol (LDL-C). Regional differences were observed between northern and southern Egypt for direct bilirubin, glucose, and high-density-lipoprotein cholesterol (HDL-C) with all their RVs lower in southern Egypt. Compared with other collaborating countries, the features of Egyptian RVs were lower HDL-C and TBil and higher TG and C-reactive protein. In addition, BMI showed weak association with most of nutritional markers. These features were shared with two other Middle Eastern countries: Saudi Arabia and Turkey. CONCLUSION: The standardized RIs established by this study can be used as common Egyptian RI, except for a few analytes that showed regional differences. Despite high prevalence of obesity among Egyptians, their RVs of nutritional markers are less sensitive to increased BMI, compared to other collaborating countries.

Evaluation of serum Nestin and HOTAIR rs12826786 C>T polymorphism as screening tools for breast cancer in Egyptian women.

BACKGROUND: Nestin is a neural stem cell protein that plays an important role in cancer stem cells (CSC) development and proliferation. It has been identified as a marker for newly formed endothelial cells and was shown to be preferentially expressed in basal and myoepithelial cells of the mammary gland. HOTAIR is long intergenic non-coding (linRNA) associated with tumorigenesis through promotion of epithelial-mesenchymal transition (EMT) and stemness as well. HOTAIR gene contains a functioning single nucleotide polymorphic site rs12826786 C>T that has been associated with several cancer types. METHODS: We evaluated serum Nestin and the HOTAIR rs12826786 C>T polymorphism in healthy Egyptian women and those with breast cancer as a possible screening tool to identify patients with breast cancer. Also, we tested the possible association of the two markers with each other and the aggressiveness of the disease. RESULTS: Patients with breast cancer had a median (Min-Max) of serum Nestin 31.3 (6.7-167.3 pg/mL), while control subjects had a median (Min-Max) of serum Nestin 42.3 (25.7-315.95) pg/mL. The best cut-off value for serum Nestin to differentiate normal subjects and patients with breast cancer was 39.9 pg/mL. This cut-off value had a diagnostic sensitivity of 84.8% and specificity of 65.1%. There was a significant difference in the distribution of different alleles in patients with breast cancer than normal subjects (P=0.039 Exact Fisher test). The breast cancer patients group had 23.9% CC, 52.1% CT, and 23.9% TT genotypes, respectively, while the control group had 46.9% CC, 42.8% CT, and 10.2% TT, respectively. CONCLUSIONS: A significantly low serum Nestin below 39.9 pg/mL and a higher percentage of the T/T homozygous variant allele of HOTAIR rs12826786 C>T were found in Egyptian patients with breast cancer. We suggest that the reported cut-off value of serum Nestin and the presence of C/T polymorphism can be used to assess the risk of females for developing breast cancer and might be of potential benefit in screening the disease. Larger studies in different ethnic groups are needed to confirm our findings.