AUTHOR=Frugé Andrew D. , Smith Kristen S. , Bail Jennifer R. , Rais-Bahrami Soroush , Demark-Wahnefried Wendy 

TITLE=Biomarkers Associated With Tumor Ki67 and Cathepsin L Gene Expression in Prostate Cancer Patients Participating in a Presurgical Weight Loss Trial

JOURNAL=Frontiers in Oncology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.544201

DOI=10.3389/fonc.2020.544201

ISSN=2234-943X

ABSTRACT=<p>Our previous presurgical weight loss trial among 40 prostate cancer patients found that rapid (but not slow) weight loss resulted in increased tumor Ki67 and <italic>Cathepsin L</italic> (<italic>CTSL</italic>) gene expression. In follow-up analyses, we strove to better understand these unexpected findings. A correlative study was undertaken by performing additional analyses [free fatty acids (FFAs), plasma <italic>CTSL</italic>, and inflammatory cytokines] on remaining pre-post intervention sera and exploring associations with extant data on tumor Ki67, body composition, physical activity (PA), and fecal microbiota. Positive associations were observed between changes in % body fat and FFAs (ρ = 0.428, <italic>p</italic> = 0.026), insulin (ρ = 0.432, <italic>p</italic> = 0.019), and Interleukin-6 (ρ = 0.411, <italic>p</italic> = 0.041). Change in Ki67 was inversely associated with change in lean mass (ρ = −0.912, <italic>p</italic> = 0.001) and change in insulin (ρ = −0.650, <italic>p</italic> = 0.042). Change in insulin was also associated with <italic>CTSL</italic> (ρ = −0.643, <italic>p</italic> = 0.024) and FFAs (ρ = −0.700, <italic>p</italic> = 0.016). Relative abundance of <italic>Bifidobacterium</italic> was associated with <italic>CTSL</italic> (ρ = 0.627, <italic>p</italic> = 0.039) and FFAs (ρ = 0.691, <italic>p</italic> = 0.019); Firmicutes was positively associated with change in PA (ρ = 0.830, <italic>p</italic> = 0.003). Contrary to hypotheses, FFAs decreased with systemic fat loss. Moreover, although glucose metabolism improved, it was inversely associated with Ki67 and <italic>CTSL.</italic> Lean mass loss was highly correlated with increased Ki67. The relationships between prostate tumor Ki67 and <italic>CTSL</italic> and weight loss associated changes in FFAs, lean mass, and fecal microbiota warrant further investigation.</p>