Changes in prostate gene expression in men undergoing an intensive nutrition and lifestyle intervention

Abstract

Epidemiological and prospective studies indicate that comprehensive lifestyle changes may modify the progression of prostate cancer. However, the molecular mechanisms by which improvements in diet and lifestyle might affect the prostate microenvironment are poorly understood. We conducted a pilot study to examine changes in prostate gene expression in a unique population of men with low-risk prostate cancer who declined immediate surgery, hormonal therapy, or radiation and participated in an intensive nutrition and lifestyle intervention while undergoing careful surveillance for tumor progression. Consistent with previous studies, significant improvements in weight, abdominal obesity, blood pressure, and lipid profile were observed (all P < 0.05), and surveillance of low-risk patients was safe. Gene expression profiles were obtained from 30 participants, pairing RNA samples from control prostate needle biopsy taken before intervention to RNA from the same patient's 3-month postintervention biopsy. Quantitative real-time PCR was used to validate array observations for selected transcripts. Two-class paired analysis of global gene expression using significance analysis of microarrays detected 48 up-regulated and 453 down-regulated transcripts after the intervention. Pathway analysis identified significant modulation of biological processes that have critical roles in tumorigenesis, including protein metabolism and modification, intracellular protein traffic, and protein phosphorylation (all P < 0.05). Intensive nutrition and lifestyle changes may modulate gene expression in the prostate. Understanding the prostate molecular response to comprehensive lifestyle changes may strengthen efforts to develop effective prevention and treatment. Larger clinical trials are warranted to confirm the results of this pilot study.

Fig. 1.

Plot of two class pairwise SAM (false discovery rate of <0.10). Forty-eight transcripts were up-regulated (red) and 453 transcripts were down-regulated (green) in morphologically normal prostate after a comprehensive diet and lifestyle intervention.

Fig. 2.

Heat map of the pre- and postintervention samples demonstrating 48 up-regulated transcripts (red in the postintervention samples) and 453 down-regulated transcripts (green in the postintervention samples) in morphologically normal prostate after a comprehensive diet and lifestyle intervention.

Fig. 3.

Waterfall plot of ratio of log (base 2) post- versus preintervention of SHOC2 gene expression comparing microarray (filled bars) to the mean of three independent replicate QRT-PCR (cross-hatched bars) measurements. No QRT-PCR data are shown for 14 of the 30 patients for whom insufficient needle biopsy RNA was available, precluding measurement.

Fig. 4.

Heat map of the gene ontology group “Intracellular Protein Traffic” illustrating the down-regulation of these 31 transcripts. Pre- and postcomprehensive diet and lifestyle intervention samples are indicated.