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

¹ Laboratory of Human Carcinogenesis and ² Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland; ³ Advanced Biomedical Computing Center, National Cancer Institute-Frederick/Science Applications International Corporation-Frederick, Inc., Frederick, Maryland; ⁴ Pathology and Laboratory Medicine, Baltimore Veterans Affairs Medical Center, Baltimore, Maryland; ⁵ Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Maryland; and ⁶ Cancer Genetic and Epidemiology Program, Lombardi Cancer Center, Georgetown University Medical Center, Washington, District of Columbia

Requests for reprints: Stefan Ambs, Laboratory of Human Carcinogenesis, National Cancer Institute, Building 37/Room 3050B, Bethesda, MD 20892-4258. Phone: 301-496-4668; E-mail: ambss{at}mail.nih.gov.

Key Words: prostate cancer • gene expression profiles • health disparity • metastasis

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 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. [Cancer Res 2008;68(3):927–36]