Abstract 4230: Transcriptomic evaluation of exercise-induced suppression of prostate cancer aggressiveness

Abstract Previous studies from our laboratory have showed that aerobic exercise significantly reduced the number of aggressive poorly differentiated tumors in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. Despite these encouraging data the underlying mechanism of how exercise reduces tumor aggressiveness remains undefined. We aimed to fill this scientific gap by utilizing a transcriptomics approach to identify potential mechanisms by which aerobic exercise suppresses prostate tumor aggressiveness. Methods: Twelve TRAMP mice, 8-10 weeks of age, were equally randomized to exercise or control group. Mice in the exercise group were singularly housed in cages with running wheels for 12 weeks. Mice in the control group maintained normal group housing and activity conditions for 12 weeks. At euthanasia, prostate tumors were excised, weighed and processed for immunohistochemistry and transcriptome analysis. Two independent pathologists, blinded to the interventions, performed histological analysis of the genitourinary mass. Outputs of sequencing data were assessed for quality and accuracy. Counts for all known mRNA, differential expression, and heatmap were prepared. Differential expression was filtered to identify genes that had a ≥2-fold change with an adjusted p<0.05. Gene ontology and pathway analyses was performed to reveal selective pathways activated. Results: No significant difference in genitourinary mass, body mass or tumor free body mass was found between groups. Pathology revealed majority of the tissue from the control group exhibited moderate to poorly differentiated tumors (3/6). On the other hand, none of the animals in the exercise intervention group showed such pathology. Four out of five showed well differentiated tumors including prostatic intraepithelial neoplasia (PIN) lesions in one animal. Transcriptomic analysis coupled with gene set enrichment identified pathways associated with triglyceride catabolic process, lipid homeostasis, lipid metabolic process, triglyceride metabolic process to be most impacted. Differentially expressed genes of interest include haptoglobin (HP) and hormone sensitive lipoprotein lipase (Lipe) were significantly lower in the exercise group. Conclusion: Our preliminary findings provide novel evidence suggesting that exercise suppresses prostate tumor aggressiveness, in part, through transcriptomic modulation and altered cellular pathways associated with intratumoral energy metabolism. This project was supported by the National Center Institute designated Mays Cancer Center at UT Health San Antonio. Citation Format: Darpan I. Patel, Paul Rivas, Yidong Chen, Zhao Lai, Robert L. Reddick, Yuji Ikeno, Rita Ghosh, A. Pratap Kumar. Transcriptomic evaluation of exercise-induced suppression of prostate cancer aggressiveness. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4230.