Abstract
The goal of this study was to evaluate prostate cancer gene expression signatures associated with elevated body mass index (BMI). Global gene expression profiles of prostate tumor cells and matching normal epithelial cells were compared between patients with features of normal and high BMI at the time of radical prostatectomy. Knowledge-based analyses revealed an association of high BMI with altered levels of lipid metabolism and cholesterol homeostasis genes, such as stearoyl-CoA desaturase 1 (SCD1) and insulin-induced gene 1 (INSIG1), respectively, in prostate tumor cells. These genes were connected to known pathways of tumorigenesis revealed by the v-maf (musculoaponeurotic fibrosarcoma) oncogene homolog (MAF), notch receptor ligand, jagged 1 (JAG1) and the alanyl aminopeptidase (ANPEP/CD13) genes. This study highlighted that SCD1, a known target of statins, may have a mechanistic role in the recently noted beneficial effects of statin treatment in reducing biochemical recurrence of prostate cancer. An additional finding of our study is that some of the obesity-related genes were upregulated in tumor-matched normal cells within the high BMI group, when compared with normal cells within the normal BMI cohort.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Adenocarcinoma / genetics*
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Adenocarcinoma / metabolism
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Adenocarcinoma / pathology
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Adenocarcinoma / surgery
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Body Mass Index*
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CD13 Antigens / genetics
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CD13 Antigens / metabolism
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Calcium-Binding Proteins / genetics
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Calcium-Binding Proteins / metabolism
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Epithelial Cells / metabolism
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Gene Expression Profiling*
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Genetic Predisposition to Disease
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Humans
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Intercellular Signaling Peptides and Proteins / genetics
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Intercellular Signaling Peptides and Proteins / metabolism
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism
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Jagged-1 Protein
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Lipid Metabolism
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Male
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Middle Aged
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Obesity / genetics*
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Obesity / metabolism
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Prostatectomy
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Prostatic Neoplasms / genetics*
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Prostatic Neoplasms / metabolism
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Prostatic Neoplasms / pathology
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Prostatic Neoplasms / surgery
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Proto-Oncogene Proteins c-maf / genetics
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Proto-Oncogene Proteins c-maf / metabolism
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Serrate-Jagged Proteins
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Stearoyl-CoA Desaturase / genetics
Substances
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Calcium-Binding Proteins
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INSIG1 protein, human
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Intercellular Signaling Peptides and Proteins
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Intracellular Signaling Peptides and Proteins
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JAG1 protein, human
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Jagged-1 Protein
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MAF protein, human
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Membrane Proteins
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Proto-Oncogene Proteins c-maf
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Serrate-Jagged Proteins
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Stearoyl-CoA Desaturase
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CD13 Antigens