Identification of immunity-related genes in prostate cancer and potential role of the ETS family of transcription factors in their regulation

Abstract

The role of the immune response in tumor progression, and disease outcome is still debated, and a lack of knowledge of the immune defenses in prostate cancer still exists. In addition, the ETS family of transcription factors which is involved in translocations frequently found in prostate cancer is reported to be essential for the regulation of immunity-related genes. In order to identify immunity-related genes in prostate cancer, we performed two microarrays using RNA extracted from laser microdissected glands of the normal prostate proper (or the peripheral zone) and moderately and poorly differentiated prostate carcinomas from patients who had undergone radical prostatectomy. Many differentially expressed genes were found, however, only immunity-related genes (B cell, innate, and T cell immunity) with an expression of more than 10-fold increase or decrease and a P<0.01 between the moderately differentiated tumors and the normal glands, and the poorly differentiated tumors and the normal glands were considered significant. Based on these two microarrays, we identified a set of 37 genes that were up- or down-regulated in tumors (moderately and poorly differentiated) compared to the normal glands. Analysis of these genes revealed, strikingly, that 31/37 of these genes have potential binding sites within their promoter regions for members of the ETS family of transcription factors, and some are reported to be targets of ETS members. These findings identified immunity-related genes in prostate cancer, and provided insights into their potential regulation, which may lead to a better early detection, immunotherapy, and therapeutic drug treatment of this disease. Unraveling the dynamics of the ETS-immunity-related genes will provide an invaluable insight into understanding prostate cancer immunology.