Expression differences between African American and Caucasian prostate cancer tissue reveals that stroma is the site of aggressive changes

In prostate cancer, race/ethnicity is the highest risk factor after adjusting for age. African Americans have more aggressive tumors at every clinical stage of the disease, resulting in poorer prognosis and increased mortality. A major barrier to identifying crucial gene activity differences is heterogeneity, including tissue composition variation intrinsic to the histology of prostate cancer. We hypothesized that differences in gene expression in specific tissue types would reveal mechanisms involved in the racial disparities of prostate cancer. We examined 17 pairs of arrays for AAs and Caucasians that were formed by closely matching the samples based on the known tissue type composition of the tumors. Using pair-wise t-test we found significantly altered gene expression between AAs and CAs. Independently, we performed multiple linear regression analyses to associate gene expression with race considering variation in percent tumor and stroma tissue. The majority of differentially expressed genes were associated with tumor-adjacent stroma rather than tumor tissue. Extracellular matrix, integrin family and signaling mediators of the epithelial-to-mesenchymal transition (EMT) pathways were all downregulated in stroma of AAs. Using MetaCore (GeneGo) analysis, we observed that 35% of significant (p<10(-3)) pathways identified EMT and 25% identified immune response pathways especially for interleukins-2, -4, -5, -6, -7, -10, -13, -15 and -22 as the major changes. Our studies reveal that altered immune and EMT processes in tumor-adjacent stroma may be responsible for the aggressive nature of prostate cancer in AAs. What's new? Disparities in prostate cancer incidence and prognosis between African Americans and Caucasians have been attributed to differences in socioeconomic status and access to health care. However, biological and genetic factors may play a role as well. This study, based on pair wise t-tests and multiple linear regression models, describes differential gene expression patterns according to race/ethnicity. Differentially expressed genes tended to be associated with tumor-adjacent stroma. The results further indicate that pathways linked to inflammation and regulation of epithelial-to-mesenchymal transition may underlie the aggressive nature of prostate cancer in African Americans.