Expression Profiling of Hereditary versus Sporadic Prostate Cancer Suggests CYR61, EGR3, KLF6 and SNF1LK as Differentially Expressed Genes

Background: Distinguishing between sub-clinical and aggressive forms of prostate cancer is difficult due to the heterogeneity of the disease. It is, however, important to identify aggressive forms to guide proper treatment. This study compared gene expression profiles in cancer cells from hereditary and sporadic prostate cancer cases and attempted to correlate differentially regulated genes with clinico-pathological characteristics and prognosis. Materials and Methods: The study population comprised patients diagnosed with clinically localized prostate cancer undergoing prostatectomy. Patients were divided into hereditary and sporadic cancer cases based on their family history. Fresh frozen biopsies from prostatectomy specimens were laser-dissected for RNA-extraction. Affymetrix HG-U133 Plus GeneChips were used to measure gene expression loaded onto Cluster 3.0 and Ingenuity Pathway Analysis softwares to examine the relationship among genes between groups. Differentially expressed genes were selected for protein expression analysis using immunohistochemistry on histological sections and tissue microarrays. Results: No single genes were signifycantly differentially expressed between hereditary and sporadic cases after adjustment for multiple testing. Using cluster analysis, four transcripts were found to be upregulated in hereditary prostate cancer tissue: CYR61, EGR3, KLF6 and SNF1LK. The intensity of CYR61, EGR2, KLF6 and SNF1LK immunostainings, however, were not significantly different in a separate sample of hereditary and sporadic prostate cancers. Furthermore, no correlations between CYR61, EGR2, KLF6, and SNF1LK staining intensities and the clinico-pathological variables or disease-free survival were detected, except for EGR3 that was significantly associated with T stage (p = 0.04). Conclusion: Overall, no single transcript level was significantly associated with hereditary prostate cancer. Cluster analysis suggested that the expression of CYR61, EGR3, KLF6 and SNF1LK were upregulated in cancer tissue from hereditary cases, but we were not able to confirm this on the protein level, and levels of these proteins were not found to correlate with clinico-pathological characteristics or biochemical recurrence.