CYP2C8 rs11572080 and CYP3A4 rs2740574 risk genotypes in paclitaxel-treated premenopausal breast cancer patients.

Breast cancer (BC) is the most prevalent malignancy in women globally. At time of diagnosis, premenopausal BC is considered more aggressive and harder to treat than postmenopausal cases. Cytochrome P450 (CYP) enzymes are responsible for phase I of estrogen metabolism and thus, they are prominently involved in the pathogenesis of BC. Moreover, CYP subfamily 2C and 3A play a pivotal role in the metabolism of taxane anticancer agents. To understand genetic risk factors that may have a role in pre-menopausal BC we studied the genotypic variants of CYP2C8, rs11572080 and CYP3A4, rs2740574 in female BC patients on taxane-based therapy and their association with menopausal status. Our study comprised 105 female patients with histologically proven BC on paclitaxel-therapy. They were stratified into pre-menopausal (n = 52, 49.5%) and post-menopausal (n = 53, 50.5%) groups. Genotyping was done using TaqMan assays and employed on Quantstudio 12 K flex real-time platform. Significant increased frequencies of rs11572080 heterozygous CT genotype and variant T allele were established in pre-menopausal group compared to post-menopausal group (p = 0.023, 0.01, respectively). Moreover, logistic regression analysis revealed a significant association between rs11572080 CT genotype and premenopausal BC. However, regarding rs2740574, no significant differences in genotypes and allele frequencies between both groups were detected. We reported a significant association between CYP2C8 genotypic variants and premenopausal BC risk in Egyptian females. Further studies on larger sample sizes are still needed to evaluate its importance in early prediction of BC in young women and its effect on treatment outcome.

Soluble CD163 impact as a prognostic biomarker in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is a malignant blood disorder in which there is an excess of white blood cells (lymphocytes) in blood and lymphoid tissues. CLL patients experience different clinical behaviors with diversity in disease course and outcome. Accordingly, prognostic markers are crucial for employing appropriate therapy protocols. CD163 (cluster of differentiation 163) is a monocyte/macrophage receptor. Soluble CD163 (sCD163) is an emerging prognostic player in the field of hematopoietic neoplasms. This study aimed to assess the prognostic potential of sCD163 as a serological marker in CLL. The study included 41 CLL patients and 44 apparently normal healthy volunteers as controls. Expression of CD38 and cytoplasmic ZAP 70 in CLL cells was assessed using flow cytometry. Beta 2 microglobulin (B2M), sCD23, and sCD163 serological markers were measured by ELISA. Serum levels of sCD163 were statistically significantly higher in CLL cases compared to controls (p=0.000). sCD163 levels were positively correlated with absolute lymphocyte count, sCD23, and B2M levels (p= 0.027, p=0.01, and p=0.004, respectively). In conclusion, levels of sCD163 in CLL is a promising prognostic tool for evaluating disease progression.

Evaluation of prognostic variables in chronic lymphocytic leukemia and association with disease stage.

The aim of the present study was to investigate different biological prognostic markers to identify high-risk patients with chronic lymphocytic leukemia (CLL) with a higher tumor burden, in order to ensure appropriate management. A total of 81 Egyptian patients with CLL were enrolled in the present study, with 75 healthy subjects serving as the control group. The expression of CD49d, CD38 and ZAP-70 in CLL cells was assessed using flow cytometry. The fluorescence in situ hybridization technique was employed to evaluate TP53 (del17p), ataxia-telangiectasia (del11q) and 13q14 (del13q14) genes and the presence of trisomy 12. The serological markers ß2 microglobulin (B2M) and sCD23 were measured by ELISA. The CD49d gene was highly expressed in 25.9% and cytogenetic aberrations were observed in 66.6% of all recruited CLL patients. The patients were categorized according to the Binet staging system and a significant increase in the expression of sCD23, CD49d and ZAP-70 was detected in group C (P=0.008, 0.034 and 0.017, respectively) when compared to groups A and B. CD49d+ patients exhibited significantly higher expression of CD38 (P=0.002) and trisomy 12 (P=0.015) and lower expression of del13q14 (P=0.001). Patients who were CD49d+ with B2M>3.5 µg/ml exhibited higher total leukocyte count (P=0.048), higher absolute lymphocyte count (P=0.036), higher expression of CD38 (P=0.002) and trisomy 12 (P=0.034) and lower expression of del13q14 (P=0.002). Therefore, sCD23, CD49d and ZAP-70 may be considered as an optimal prognostic marker combination to be evaluated in the early stages of CLL and throughout disease management. Integrating both serological markers and CD49d expression by flow cytometry may add to the prognostic value of each marker alone and help identify high-risk patients with a higher tumor burden.

Altered Expression of MicroRNAs in the Bone Marrow of Multiple Myeloma Patients and their Relationship to Cytogenetic Aberrations.

BACKGROUND: Multiple Myeloma (MM) is a complex hematologic malignancy, driven by several genetic and epigenetic alterations. MiRNAs as biomarkers have become a rapidly growing research area in the last decade. AIM: The aim was to study the expression pattern of selected miRNAs and to explore the impact of cytogenetic aberrations in MM patients for therapeutic tools. PATIENTS AND METHODS: Forty Egyptian adult patients were selected for the study with symptomatic newly diagnosed MM disease. Bone marrow samples were collected to investigate twelve miRNAs selected according to their relation to the most common cytogenetic aberrations with relevant prognostic value. The relative expression of the selected miRNAs was determined using a real-time PCR technique. Fluorescence In Situ Hybridization (FISH) technique was performed for cytogenetic analysis. RESULTS: Eight miRNAs were down-regulated [miR-15a (p<0.001), miR214-3p (p<0.001), miR135b (p<0.001), miR19a-3p (p<0.001), miR19b-3p ((p=0.026), miR30e-5p (NS), miR133a (NS), miR146a- 5p (p<0.001)]. Four miRNAs were up-regulated [miR99b-5p (p=0.028), miR125a-3p (p=0.004), let7b- 5p (p<0.001), let7c-5p (p<0.001)]. Significant relation was observed between positive 14q32 rearrangement using the break apart re-arrangement probe for 14q32.33 locus and lower expression levels of miR15a (p= 0.014), 214-3p (p=0.046), 99b-5p (p=0.014), 146a-5p (p=0.041). A higher expression level of miR30e-5p was significantly related to positive 14q32 rearrangement. CONCLUSION: Deregulated miRNAs were identified and the association with 14q32 rearrangement and MM pathogenesis has been determined.