Exploration of biomarkers from a pilot weight management study for men undergoing radical prostatectomy

Autor: James R. Hébert, Harsh B. Pathak, Prabhakar Chalise, William P. Parker, Jill Hamilton-Reeves, Mohamad Dave Dimachkie, John DiGiovanni, Hilary L. Robertson, Carrie Michel, Debra K. Sullivan, Andrew K. Godwin, Misty D. Bechtel, Nitin Shivappa, Eugene K. Lee, J. Brantley Thrasher
Rok vydání: 2020
Předmět:
Zdroj: Urol Oncol
ISSN: 1873-2496
Popis: BACKGROUND: Several biologic mechanisms, including inflammation and immune changes, have been proposed to explain the role of obesity in prostate cancer (PCa) progression. Compared to men of a healthy weight, overweight and obese men are more likely to have PCa recurrence post-prostatectomy. Obesity is related to inflammation and immune dysregulation; thus, weight loss may be an avenue to reduce inflammation and reverse these immune processes. OBJECTIVES: This study explores the reversibility of the biological mechanisms through intentional weight loss using a comprehensive weight management program in men undergoing prostatectomy. Outcomes include blood and tissue biomarkers, microtumor environment gene expression, inflammation markers and Dietary Inflammatory Index (DII) scores. METHODS: Twenty overweight men undergoing prostatectomy participated in this study. Fifteen men chose the intervention and five men chose the non-intervention group. The intervention consisted of a comprehensive weight loss program prior to prostatectomy and a weight maintenance program following surgery. Prostate tissue samples were obtained from diagnostic biopsies before the intervention and prostatectomy samples after weight loss. Blood samples and diet records were collected at baseline, pre-surgery after weight loss and at study end after weight maintenance. Immunohistochemistry (IHC) and NanoString analysis were used to analyze the tissue samples. Flow cytometry was used to assess circulating immune markers. Inflammation markers were measured using Luminex panels. RESULTS: The intervention group lost >5% body weight prior to surgery. DII scores improved during the weight loss intervention from baseline to pre-surgery (P=0.002); and between group differences were significant (P=0.02). DII scores were not associated with IL-6 nor hsCRP. In the intervention, CXCL12, CXCR7 and CXCR4 (C-X-C motif chemokine ligand/receptor) and Ki67 expression decreased in the prostate tissue from biopsy to surgery (P=0.06), yet plasma CXCL12 increased during the same timeframe (P=0.009). The downregulation of several genes (FDR
Databáze: OpenAIRE