Protein profiling studies of
prostate cancer have been widely used to characterize molecular differences between diseased and non-diseased tissues. When combined with pathway analysis, profiling approaches are able to identify molecular mechanisms of
prostate cancer, group patients by
cancer subtype, and predict prognosis. This strategy can also be implemented to study
prostate cancer in very specific populations, such as African Americans who have higher rates of
prostate cancer incidence and mortality than other racial groups in the United States. In this study, age-, stage-, and Gleason score-matched prostate
tumor specimen from African American and Caucasian American men, along with non-malignant adjacent prostate tissue from these same patients, were compared.
Protein expression changes and altered pathway associations were identified in
prostate cancer generally and in African American
prostate cancer specifically. In comparing
tumor to non-malignant samples, 45
proteins were significantly
cancer-associated and 3
proteins were significantly downregulated in
tumor samples. Notably,
fatty acid synthase (FASN) and epidermal
fatty acid-binding protein (FABP5) were upregulated in human
prostate cancer tissues, consistent with their known functions in
prostate cancer progression.
Aldehyde dehydrogenase family 1 member A3 (ALDH1A3) was also upregulated in
tumor samples. The
Metastasis Associated
Protein 3 (MTA3) pathway was significantly enriched in
tumor samples compared to non-malignant samples. While the current experiment was unable to detect statistically significant differences in
protein expression between African American and Caucasian American samples, differences in overrepresentation and pathway enrichment were found. Structural components (
Cytoskeletal Proteins and
Extracellular Matrix Protein protein classes, and Biological Adhesion Gene Ontology (GO) annotation) were overrepresented in African American but not Caucasian American
tumors. Additionally, 5 pathways were enriched in African American prostate
tumors: the
Small Cell Lung Cancer, Platelet-
Amyloid Precursor
Protein,
Agrin, Neuroactive
Ligand-Receptor Interaction, and Intrinsic pathways. The
protein components of these pathways were either basement membrane
proteins or coagulation
proteins.