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.
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Acknowledgements
We thank Ms Lakshmi Ravindranath and Ms London Toney for the superb technical assistance, Mr Zhe Chang and Ms Sally Elsamanoudi for the medical informatics support, Mr Stephen Doyle for the outstanding art work and Ms Tia Morris for editorial comments. This work was funded by the CPDR through an ongoing grant from the US Army Medical Research and Materiel Command and the NIH grant RO1 DK065977 to SS and GP.
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Sharad, S., Srivastava, A., Ravulapalli, S. et al. Prostate cancer gene expression signature of patients with high body mass index. Prostate Cancer Prostatic Dis 14, 22–29 (2011). https://doi.org/10.1038/pcan.2010.44
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DOI: https://doi.org/10.1038/pcan.2010.44
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