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Introduction: Obesity is one of the largest medical challenges in the USA. Recent studies highlighted the association of obesity with prostate cancer aggressiveness. However, obesity-associated gene expression alterations need to be better understood. The Objective of this study was to evaluate elevated BMI-associated prostate cancer gene expression signatures.
Materials & Methods: Prostate cancer cells and matching non-adjacent normal epithelial cells were selected by laser capture microdissection from frozen radical prostatectomy specimens of patients with normal- and high BMI. Gene expression analyses were performed by using HG-U133A Affymetrix microarrays. Tumor-over-normal gene expression ratios were calculated and data were further analyzed by applying a three-fold cutoff. To pinpoint central regulatory nodes of gene expression alterations knowledge-based pathway analysis, gene ontology and comparative meta-analysis of obesity related independent datasets were performed.
Results: Bioinformatic analyses revealed associations of high BMI with cholesterol and lipid metabolism associated genes within fatty acid synthesis and oxidation-reduction pathways. The identified high BMI-associated genes were tightly connected to genes involved in lipid metabolism, cholesterol homeostasis, and tumorigenesis. The analysis highlighted the association of stearoyl-CoA desaturase (SCD1) with elevated BMI.
Conclusions: Our study revealed that SCD1, a known target of atorvastatin, may play a mechanistic role in the recently noted beneficial effects of statin treatment in reducing biochemical recurrence of prostate cancer.