Background: Metastatic breast cancer (MBC) represents a major health problem in Egypt and worldwide. Prognostic and predictive factors for patients with MBC are highly required for better management and improved survival. The aim of this study was to assess the prognostic and predictive value(s) of CYP2D6 polymorphisms in Tamoxifen responders and non-responders. Methods: A cohort of 157 hormone receptor positive, locally recurrent inoperable and/or metastatic (MBC) Egyptian female patients was assessed for CYP2D6 polymorphisms. Data were correlated to relevant clinic-pathological features of the patients, response to tamoxifen, and survival rates. Results: CYP2D6 polymorphisms were detected in 44/157 cases (28%), 30 of them (68.2%) were refractory and 14 (31.8%) were responders (P=0.027). The CYP2D6 *3,*4 variants were significantly prevalent in the refractory group 26/30 (86.6%), while the *10/*10 and *10/*3 variants were more common in the responders 12/14 (85.71%, P=0.027). CYP2D6 polymorphism associated significantly with Her-2 amplification (P=0.001) as well as reduced overall survival rates in both refractory and responder patients (P< 0.001). Conclusion: CYP2D6 polymorphisms can significantly predict response to Tamoxifen treatment, and also associates with poor overall survival rates in MBC patients.
Background: Serum Prostate-specific antigen (PSA) has been used for screening and diagnosis of prostate cancer (PCa) but it is burdened by its low accuracy, creating a need for reliable diagnostic markers. Despite prostate-specific membrane antigen (PSMA) and prostate stem cell antigen (PSCA) being widely expressed in the tissue of PCa, no definite conclusion regarding their use as clinical biomarkers due to their lacking organ specificity. Therefore, this study aimed to evaluate the peripheral blood levels of PSMA and PSCA mRNAs and examine their diagnostic significance as non-invasive integrated markers. Materials and Methods: 125 subjects were enrolled in this study. They were divided into 25 healthy controls, 25 BPH patients, and 75 PCa patients. The expression levels of PSMA and PSCA were determined using quantitative RT-PCR, in addition to measuring serum PSA. Results: Levels of PSMA and PSCA were over-expressed in PCa patients compared to controls and BPH patients and were found to be associated with increased susceptibility to PCa. Moreover, the diagnostic values of PSMA and PSCA to distinguish PCa patients from BPH patients and controls were inferior to that of PSA. However, the combination of PSMA and PSCA with PSA enhanced the efficacy of the latter. Conclusion: This study suggests that these genes were associated with malignant susceptibility. Concerning the duality of PSMA-PSA or PSCA-PSA, this implies the significance of their investigation together in peripheral blood of prostate patients.
BackgroundProstate cancer (PC) incidence has risen globally. As there are no current independent biomarkers with high diagnostic efficiency to detect PC, this study was performed to investigate the relative gene expression levels of E2F3 and survivin in the whole blood of PC, benign prostate hyperplasia (BPH), and normal control individuals and to explore their diagnostic value.Material and methodsParticipants of the study were divided into three groups; normal control group (n=25), BPH patients (n=25), and PC patients (n=75). The E2F3 and survivin gene expression levels were assessed using real-time qPCR in addition to the measurement of free and total levels of prostate-specific antigen (PSA) using electrochemiluminescence assays.ResultsSurvivin relative gene expression was over-expressed in PC and BPH patients compared to the normal control group, whereas, E2F3 did not differ significantly among the studied groups. Compared to PSA, E2F3 and survivin mRNA expression levels had lower diagnostic efficacy to differentiate PC from normal and BPH individuals with an area under curve (AUC) of 0.471 and 0.727, respectively. Further, survivin expression level was associated with increased the risk of PC.ConclusionSurvivin and E2F3 relative expression levels in peripheral blood had low diagnostic performance to detect PC and individuals with high survivin expression levels may have higher risk to develop PC.
Background Metastatic breast cancer (MBC) is a major health problem worldwide. Some patients improve on tamoxifen and others do not respond to treatment. Therefore, the aim of the current study is to assess genetic aberrations in the Her2/EGFR-PDGFR pathway associated with tamoxifen response in MBC patients. Methods This is a retrospective cohort study, including 157 hormone receptors positive, locally recurrent inoperable and/or MBC patients on tamoxifen treatment. Patients were categorized into 78 (49.7%) tamoxifen responders and 79 (50.3%) tamoxifen non-responder patients. Genetic aberrations of 84 genes involved in the Her2/EGFR-PDGFR pathway were assessed in the tumor tissue samples obtained from the patients using SA-Bioscience assay. The identified panel was correlated to patients’ response to treatment, to detect the differentially expressed genes in tamoxifen responders and non-responders. Results One hundred twenty-three (78.3%) patients were estrogen receptor (ER) and progesterone receptor (PR) positive, 108 (68.8%) were ER only positive, and 78 (49.7%) were PR only positive. There were 56 genes overexpressed in the refractory group compared to responders. However, only five out of these 56 genes, Janus kinase 1 (JAK1), collagen type I alpha 1 (COL1A1), GRB2-associated binding protein 1 (GAB1), fibronectin-1 (FN1), and MAP kinase-interacting serine/threonine-protein kinase (MKNK1), showed statistical significance between the two groups. Patients with bone metastasis showed a better response to treatment compared to those with metastatic deposits in other sites such as visceral metastasis (P < 0.005). Conclusions Genetic profiling using simple quantitative real-time polymerase chain reaction (qRT-PCR) protocols could be used to assess response to tamoxifen treatment in MBC patients. According to our data, a five-gene panel in the EGFR pathway (JAK1, COL1A1, GAB1, FN1 and MKNK1) could be used to categorize MBC patients into groups according to treatment response.
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