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Publications (2)6.09 Total impact

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    ABSTRACT: ERG-gene rearrangement defines a distinct molecular subtype of PCA with potential biological and clinical implications. To identify a molecular signature reflective of the downstream effects of ERG-mediated transcriptional regulation with prognostic implication in patients with prostate cancer (PCA). We used a singular value decomposition (SVD) bioinformatics approach to re-analyse gene expression data previously generated from 46 prostate tumours, and identified an ERG-like gene signature. The signature was validated on several patient cohorts and individual genes were correlated to ERG expression and PCA progression. An ERG-like 10-gene signature was identified and validated in PCA cohorts of the physician health study (p115) (n = 110) in addition to three independent public datasets, and was significantly associated with disease progression, biochemical recurrence and PCA-specific mortality. Patients with the ERG-like signature were significantly associated with disease recurrence on univariate (hazard ratio [HR] 2.6; 95% confidence interval [CI]:1.3-5.2; P = 0.004) and multivariate analysis (HR 2.3; 95% CI:1.1-4.6, P = 0.016) compared with patients without this signature. Within the group of patients with Gleason score (GS) 6 and 7 PCA, the signature added prognostic value beyond GS and identified patients at higher risk of cancer deaths more accurately than GS alone or in combination with ERG status. Protein expression of the 10 genes were significantly associated with ERG and disease progression regardless of ERG status. The characterized ERG-like signature was reflective of aggressive features of ERG-mediated transcription and was prognostically robust. The combination of this signature with clinicopathological variables should be validated prospectively to explore its clinical utility in stratifying patients with PCA and in identifying those at higher risk of metastatic and lethal disease.
    BJU International 06/2013; · 3.05 Impact Factor
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    ABSTRACT: • To investigate the effects of different folic acid concentrations on the growth and invasiveness of prostate cancer cell lines. • To determine if observed changes are correlated with changes in levels of the potential prostate cancer biomarker, sarcosine, a byproduct of folate metabolism. • The prostate cancer cell lines PC-3, LNCaP and DU145 were cultured in media containing 4, 20 or 100 nm of folic acid and assayed for growth over 9 days by counting viable cells at 3-day intervals, or for invasion by passage through a Matrigel-coated transwell membrane. • Cells grown in the different folic acid media were collected and subjected to metabolomic analysis by gas chromatography and mass spectrometry to measure levels of intracellular sarcosine. • The results show that higher levels of folic acid can increase cell growth in PC-3 and LNCaP prostate cancer cell lines, and may also increase the invasive capacity of PC-3, LNCaP and DU145 cells. • We did not observe a correlation between increased invasion from higher folic acid concentrations and levels of sarcosine, but there were significant changes in other metabolites in cells grown in higher levels of folic acid. • These findings suggest that folic acid has an important and potentially negative role in prostate cancer progression.
    BJU International 07/2011; 109(5):788-95. · 3.05 Impact Factor