Browsing by Author "Bismar, Tarek A."

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    ARPC1B Gene: As a Potential Novel Prostate Cancer Driver
    (2019-12) Zaaluk, Hend; Bismar, Tarek A.; Riabowol, Karl T.; Argiropoulos, Bob; Lees-Miller, Susan; Eszlinger, Markus
    Prostate cancer is the most common malignancy in men and the second leading cause of cancer-related deaths in western countries. Currently, there is a lack of specific molecular markers that can predict cancer progression and prognosis. Characterization of prostate cancer driver genes is essential for investigating the cellular changes that influence the progression of cancer. This will provide a better understanding to prostate cancer carcinogenesis, elucidate novel biomarkers, and improve clinical outcomes. Previously our lab performed a bioinformatics screen using several public cohorts and identified a panel of genes that are deregulated on the mRNA and DNA levels. We hypothesize that these gene are potentially acting as oncogenes and tumor suppressors that could be related to the prognosis of prostate cancer. Actin-related protein -2/3 subunit B (ARPC1B) was found to be one of the most highly dysregulated genes. Dysregulation of ARPC1B expression has been detected in multiple human cancers and ARPC1B protein has been implicated in the control of actin polymerization. Moreover, ARPC1B is involved in many pathways such as cytoskeleton remodeling via actin; integrin mediated cell adhesion and movement of cell/subcellular compartments. The purpose of this research was to evaluate the expression levels of ARPC1B in different prostate cancer cell lines and investigate its potential role in disease progression. ARPC1B expression was analysed using western blot and qRT-PCR in multiple cell lines. We found ARPC1B protein and mRNA levels to be upregulated in the PC3 cell line compared to other cell lines. To validate the role of ARPC1B, siRNA was used to knockdown ARPC1B in PC3 cells which resulted in significant reduction of cell proliferation as measured using the MTS assay. Reduced cell growth and/or reduced migration in cells with ARPC1b knocked down was also seen using scratch assays. Tissue expression levels were also investigated on a progression tissue microarray and showed increased intensity with disease progression from benign to localized cancer and castrate resistant disease. These data suggest that ARPC1B could be a valid prostate cancer marker.
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    Coordinate MicroRNA-Mediated Regulation of Protein Complexes in Prostate Cancer
    (Public Library of Science, 2013-12-31) Alshalalfa, Mohammed; Bader, Gary D.; Bismar, Tarek A.; Alhajj, Reda
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    Detecting Cancer Outlier Genes with Potential Rearrangement Using Gene Expression Data and Biological Networks
    (2012-06-28) Alshalalfa, Mohammed; Bismar, Tarek A.; Alhajj, Reda
    Gene alterations are a major component of the landscape of tumor genomes. To assess the significance of these alterations in the development of prostate cancer, it is necessary to identify these alterations and analyze them from systems biology perspective. Here, we present a new method (EigFusion) for predicting outlier genes with potential gene rearrangement. EigFusion demonstrated excellent performance in identifying outlier genes with potential rearrangement by testing it to synthetic and real data to evaluate performance. EigFusion was able to identify previously unrecognized genes such as FABP5 and KCNH8 and confirmed their association with primary and metastatic prostate samples while confirmed the metastatic specificity for other genes such as PAH, TOP2A, and SPINK1. We performed protein network based approaches to analyze the network context of potential rearranged genes. Functional gene rearrangement Modules are constructed by integrating functional protein networks. Rearranged genes showed to be highly connected to well-known altered genes in cancer such as AR, RB1, MYC, and BRCA1. Finally, using clinical outcome data of prostate cancer patients, potential rearranged genes demonstrated significant association with prostate cancer specific death.
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    Detecting Cancer Outlier Genes with Potential Rearrangement Using Gene Expression Data and Biological Networks
    (Hindawi Publishing Corporation, 2012-05-08) Alshalalfa, Mohammed; Bismar, Tarek A.; Alhajj, Reda
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    ERG Protein Expression Is of Limited Prognostic Value in Men with Localized Prostate Cancer
    (2013-08-19) Teng, Liang Hong; Wang, Cheng; Dolph, Michael; Donnelly, Bryan; Bismar, Tarek A.
    Background. The prognostic significance of ERG expression in prostate cancer (PCA) has generated mixed results. We sought to investigate the prognostic significance of ERG expression in a localized cohort of men with PCA. Material and Methods. We investigated ERG protein expression in a cohort of 198 men with localized PCA. ERG expression was correlated with patients' clinical outcome and several pathological parameters, including Gleason score (GS), pathological stage, surgical margin, and extra-capsular extension. Results. ERG expression was detected in 86/198 (43.4%) patients exclusively in neoplastic epithelium. Overall, ERG mean expression intensity was versus in acinar PCA compared to foamy type PCA (). In HGPIN, ERG intensity levels were comparable to those in foamy type PCA () but significantly lower than those in acinar PCA (). ERG expression was significantly associated with extra-prostatic extension and higher pathological stage and showed a trend toward seminal vesicle invasion. Herein, ERG expression was documented in 50/131 (38.1%) patients with pT2 versus 30/55 (54.5%) patients with pT3 (). ERG association with higher pathological stage was more pronounced in patients with . Grouping patients into those with versus 7, there was no significant association between ERG expression and GS. Similarly, no association was present in relation to either surgical margins or postsurgical serum PSA levels. Conclusion. We report significant association between ERG protein levels and extra-prostatic extension and higher pathological stage. ERG expression is not associated with adverse clinical outcome and is of limited prognostic value in localized PCA.