Expression differences between African American and Caucasian prostate cancer tissue reveals that stroma is the site of aggressive changes - PubMed (original) (raw)

. 2014 Jan 1;134(1):81-91.

doi: 10.1002/ijc.28326. Epub 2013 Jul 13.

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

Matthew A Kinseth et al. Int J Cancer. 2014.

Abstract

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.

Keywords: EMT; immune response; prostate cancer; racial disparity; stroma expression.

© 2013 UICC.

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Conflict of interest statement

Financial Disclosures and conflict of interest: D. Mercola is a board member of Proveri Inc. which has a license from the Regents of the University of California for the development of clinical assays for prostate cancer. The other authors declare they have no conflict of interest with this publication.

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