The effect of short-term soy isoflavone supplementation on mRNA in localized prostate cancer

Abstract

Background: Soy isoflavones have been hypothesized to affect gene expression related to prostate cancer development and progression, yet few studies have evaluated the effect of this phytochemical on the transcriptome of prostate cancer cells in a human model. Objective: To determine if short-term soy isoflavone supplementation influences gene expression in men with localized prostate cancer. Methods: Six men diagnosed with clinically localized prostate cancer were asked to take a soy isoflavone supplement for up to 6 weeks prior to radical prostatectomy. Total RNA was isolated and sequenced from tumor and adjacent normal frozen prostate tissue pairs obtained from these participants. Gene expression profiles were determined, differentially expressed genes were identified, and gene expression profiles were mapped to molecular pathways for biological interpretation using Ingenuity Pathway Analysis software. The trimmed mean of the M values method (TMM, where M=log2 fold change) was used to calculate the normalization factor. Quantile-adjusted conditional maximum likelihood (qCML) method was used to estimate common dispersion across all genes. Exact test with a negative binomial distribution was used to calculate expression differences between groups. Multiple test adjustments were carried out using the false discovery rate (FDR) using Benjamini and Hochberg's method. An FDR value of <0.05 was considered statistically significant. Results: All 6 men were included in the final analysis. Soy isoflavones differentially expressed 128 genes in cancerous prostate tissue and 166 genes in normal prostate tissue. Twenty genes were differentially expressed in both tissues, 2 of which were differentially regulated by soy in different tissues. Some pathways suggested a protective effect (human embryonic stem cell pluripotency, complement system, protein citrullination, and methylglyoxal degardation VI pathways), while others suggested harm (intrinsic and extrinsic prothrombin activation and IL-17A pathways). The following pathways were of unknown relevance: acute phase response signaling, UDP-glucuronosyltransferase, and glutamate-dependent acid resistance pathways. Conclusion: Short-term soy isoflavone supplementation prior to curative treatment for localized prostate cancer was found to significantly affect gene expression in tumor and adjacent normal prostate tissues.