Tumor Immunobiological Differences in Prostate Cancer between African-American and European-American Men

Tiffany A Wallace,Harris G Yfantis,Robert M Stephens,Stefan Ambs,Ming Yi,John W Gillespie,Neil E Caporaso,Robyn L Prueitt,Christopher A Loffredo,Tiffany M Howe

doi:10.1158/0008-5472.can-07-2608

Abstract

The incidence and mortality rates of prostate cancer are significantly higher in African-American men when compared with European-American men. We tested the hypothesis that differences in tumor biology contribute to this survival health disparity. Using microarray technology, we obtained gene expression profiles of primary prostate tumors resected from 33 African-American and 36 European-American patients. These tumors were matched on clinical variables. We also evaluated 18 nontumor prostate tissues from seven African-American and 11 European-American patients. The resulting datasets were analyzed for expression differences on the gene and pathway level comparing African-American with European-American patients. Our analysis revealed a significant number of genes, e.g., 162 transcripts at a false-discovery rate of <or=5% to be differently expressed between African-American and European-American patients. Using a disease association analysis, we identified a common relationship of these transcripts with autoimmunity and inflammation. These findings were corroborated on the pathway level with numerous differently expressed genes clustering in immune response, stress response, cytokine signaling, and chemotaxis pathways. Several known metastasis-promoting genes, including autocrine mobility factor receptor, chemokine (C-X-C motif) receptor 4, and matrix metalloproteinase 9, were more highly expressed in tumors from African-Americans than European-Americans. Furthermore, a two-gene tumor signature that accurately differentiated between African-American and European-American patients was identified. This finding was confirmed in a blinded analysis of a second sample set. In conclusion, the gene expression profiles of prostate tumors indicate prominent differences in tumor immunobiology between African-American and European-American men. The profiles portray the existence of a distinct tumor microenvironment in these two patient groups.

Highlights

Prostate cancer is the most frequently diagnosed malignancy and the second leading cause of cancer mortality in men older than 40 years in the United States [1]
African-American men have the highest risk of developing prostate cancer, and due to the manifestation of a more aggressive disease, they have over twice the mortality rate of European-American men [3, 4]
Prostate tumors were collected from 33 African-American and 36 European-American patients with localized disease

Summary

Introduction

Prostate cancer is the most frequently diagnosed malignancy and the second leading cause of cancer mortality in men older than 40 years in the United States [1]. Whereas socioeconomic factors contribute to this health disparity [4, 5], they do not fully explain the differences in prostate cancer incidence, aggressiveness, and mortality among different race/ ethnic groups in the United States [6, 7]. The chromosomal region of 8q24 has been strongly implicated as a site of prostate cancer susceptibility [12, 13] In these studies, men of African ancestry were found to carry at-risk alleles at a higher frequency than men of European ancestry. Men of African ancestry were found to carry at-risk alleles at a higher frequency than men of European ancestry Those results indicate that genetic factors may account for some of the excess prostate cancer risk that African-American men experience when compared with other race/ethnic groups

Methods

Results

Conclusion