ASPO Abstracts

Biomarkers associated with tumor Ki67 and Cathepsin L gene expression in prostate cancer patients participating in a weight loss trial

Authors: Frugé AD, Smith KS, Bail JR, Rais-Bahrami S, Demark-Wahnefried W

Category: Lifestyles Behavior, Energy Balance & Chemoprevention
Conference Year: 2020

Abstract Body:
Purpose: Our previous presurgical weight loss trial among 40 men with prostate cancer found that rapid (but not slow) weight loss resulted in increased tumor Ki67, as well as increased Cathepsin L (CTSL) expression. In follow- up analyses, we strove to better understand these unexpected findings. Methods: Pre- and post-intervention free fatty acids (FFA) and inflammatory cytokines from 27 men with adequate sera were analyzed, and studied in relation to Ki67, body composition, physical activity (PA), fecal microbiota and tumor gene expression data for both the weight-loss intervention (WLI) and control study arms. Cross-sectional and longitudinal associations between biomarkers were assessed with Spearman correlations. Paired sample t- tests compared within group changes in biomarkers. Analysis of covariance was used to assess between group changes in the subsample of participants (n=12) with gene expression data. Results: Positive associations were observed between changes in percent body fat and serum FFA (ρ=0.428, p=0.026) as well as Interleukin-6 (ρ=0.411, p=0.041). In the gene expression subset, WLI lost more weight (-6.8kg vs. -0.3kg, p=0.002) and lean mass (-1.8kg vs. 0.2kg, p=0.029), and had increased Ki67 (+5% vs. -8.1%, p=0.001), with no differences between groups in PA, caloric and macronutrient intake, or inflammatory cytokines. Change in Ki67 was inversely associated with change in lean mass (ρ=-0.887, p=0.001) and change in serum insulin (ρ=-0.650, p=0.042). Change in insulin was also associated with CTSL (ρ=-0.643, p=0.024) and FFA (ρ=-0.700, p=0.016). Relative abundance of the genus Bifidobacterium was associated with CTSL (ρ=0.627, p=0.039) and FFA (ρ=0.691, p=0.019); relative abundance of Firmicutes was positively associated with change in PA (ρ=0.830, p=0.003). Conclusions: Contrary to our hypothesis, FFA decreased with fat loss; glucose metabolism improved and was inversely associated with Ki67 and CTSL. Given these findings and the potential role of the microbiota, the relationship between prostate tumor expression of CTSL and weight-loss associated changes in FFA warrant further investigation.

Keywords: prostatic neoplasms, weight loss, Cathepsin L, microbiota