Abstract 372: Obesity matters: Prostate cancers that overexpress fatty acid binding protein 5 are more common in men who are overweight or obese
Authors: Sandra M. Gaston, Soroush Rais-Bahrami, James Kearns, Dennis Otali, Denise Oelschlager, Mark S. DeGuenther, Jeffrey W. Nix, Peter N. Kolettis, James E. Bryant, Robert A. Oster, William E. Grizzle
Journal: Cancer Research (2018)

Abstract BACKGROUND: One of the hallmarks of the malignant phenotype is an increase in the cell's demand for fatty acids (FA). Many cancers, including prostate cancer, show increased expression of fatty acid synthase (FASN), a multi-component enzyme that catalyzes the de novo synthesis of the fatty acid palmitate. However recent observations suggest that alternate mechanisms for FA acquisition are also important, including the utilization of exogenous palmitate when it's available. Recently, through a biopsy-based molecular analysis of high risk prostate cancer, we identified a tumor subtype with very high (&amp;gt;10 fold) "outlier" overexpression of fatty acid binding protein 5 (FABP5). FABP5 is involved in lipid transport and signaling, and it facilitates the utilization of palmitate and other FAs from outside of the cell. De novo palmitate synthesis by the FASN pathway is energetically expensive compared to utilization of exogenous fatty acids. STUDY DESIGN: We proposed that prostate cancers that can efficiently utilize exogenous palmitate are at a selective advantage when dietary FAs are abundant. In this study, to test that hypothesis, we compared FABP5 and FASN expression levels in prostate cancers obtained from diagnostic biopsies from normal weight, overweight and obese study subjects. A total of 201 consecutive eligible prostate biopsy patients were prospectively enrolled; 151 (75%) of these patients were cancer positive. Prostate cancer FABP5 and FASN mRNA expression were measured by qrtPCR and FABP5/FASN and FASN/FABP5 expression ratios were determined for each cancer positive core. BMI and self-identified race were obtained from hospital records. RESULTS: The expression of FABP5 and the FABP5/FASN expression ratio were significantly higher in overweight and obese individuals compared to normal weight individuals (mean FABP5/FASN overexpression ratio of 20.2 in overweight/obese subjects vs 4.0 in normal weight subjects; p &amp;lt; 0.05). The highest levels of prostate cancer FABP5 outlier overexpression (FABP5/FASN &amp;gt; 100) were observed in African American subjects with BMI &amp;gt; 30, and high levels of FABP5 outlier overexpression were more strongly associated with overall Gleason sum in African American than in European American subjects. CONCLUSIONS: In our study population, prostate cancer subtypes with high levels of FABP5 overexpression were more common in biopsy patients who were overweight or obese compared to normal weight patients. The highest levels of FABP5 overexpression in were observed in prostate cancers from obese African American subjects. Such FABP5 dominant prostate cancers may utilize exogenous fatty acids more efficiently and be more sensitive to dietary interventions than the more widely studied FASN dominant prostate cancers. Funding: DOD Prostate Cancer Research Program Awards W8XWH-10-1-0543 (Grizzle, PI) and W81XWH-10-1-0544 (Gaston, PI) Citation Format: Sandra M. Gaston, Soroush Rais-Bahrami, James Kearns, Dennis Otali, Denise Oelschlager, Mark S. DeGuenther, Jeffrey W. Nix, Peter N. Kolettis, James E. Bryant, Robert A. Oster, William E. Grizzle. Obesity matters: Prostate cancers that overexpress fatty acid binding protein 5 are more common in men who are overweight or obese [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 372.