Abstract
Introduction: Prostate cancer (PCa) is the most prevalent cancer among men and the third most common cause of cancer related-deaths in the USA. Clinically, PCa is a heterogeneous disease ranging from indolent asymptomatic cases to very aggressive life threatening forms. The most critical clinical challenge in the management of the patients is identifying those individuals at risk of developing metastatic disease. Positive family history and African American ancestry are two of the most important recognized risk factors for PCa. African American (AA) men have disproportionately high incidence and mortality rates of PCa when compared to Caucasian American (CA) men and other ethnic groups in the USA. The molecular basis of this disparity is unknown and our long term objective is to identify the molecules and characterize the mechanisms that are involved in PCa aggressiveness in African American populations. Potential biomarkers for progression of PCa from the precursor lesion to organ confined primary tumor and finally to distant metastasis may include genes, proteins and metabolites. The identification of biomarkers that contribute to this disparity could potentially improve diagnosis, prognosis and allow for better clinical management decisions in PCa.
Methods: We have analyzed protein expression in prostate cancer cells lines with different ethnic backgrounds using high throughput liquid chromatography tandem quantitative mass spectrometry. Validations of the most significantly differentially expressed proteins were done by Western blot and qRT-PCR. Characterization of the target proteins was carried out by performing siRNA knockdowns, proliferation assays and invasion assays, flow cytometry, Western blot and immunofluorescence assays.
Results: We demonstrate for the first time differential expression of specific classes of proteins between Caucasian and African American derived prostate cancer cells with the same tumorigenic phenotypes. The most significantly differentially upregulated proteins in the proteomics experiments were validated by Western blot, confocal microscopy and immunohistochemistry. SiRNA knockdown of target proteins suppress the growth, invasive and migratory capacity of the malignant cells and results in the modulation of various signal transduction pathways.
Conclusions: We demonstrate the differential expression of specific classes of proteins in prostate cancer cell lines with different ethnic and tumorigenic phenotypes. Some of these proteins may play a role in the progression, aggression and metastasis of PCa. These findings are currently being validated using disease stratified tissue microarrays to determine the expression patterns of these proteins in PCa patients. We are currently focusing on uncovering the potential mechanisms responsible for progression and aggression of PCa that are modulated by these proteins. These studies may provide novel avenues for the development of new personalized cancer therapies, cancer diagnosis, prognosis, and early detection in African American populations that are currently disproportionally impacted by aggressive forms of prostate cancer.
Citation Format: Tanya C. Burch, Julius O. Nyalwidhe. Comparative proteomics analysis of ethnically stratified prostate cancer cells reveal potential markers of disparities. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr C20. doi:10.1158/1538-7755.DISP13-C20
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