Department of Urology, University of Kansas Medical Center, Kansas City, KS.
Department of Dietetics & Nutrition, University of Kansas Medical Center, Kansas City, KS.
Urol Oncol. 2021 Aug;39(8):495.e7-495.e15. doi: 10.1016/j.urolonc.2021.01.010. Epub 2021 Feb 7.
Several biologic mechanisms, including inflammation and immune changes, have been proposed to explain the role of obesity in prostate cancer (CaP) progression. Compared to men of a healthy weight, overweight and obese men are more likely to have CaP 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.
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.
Twenty overweight men undergoing prostatectomy participated in this study. Fifteen men chose the intervention and 5 men chose the nonintervention 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 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.
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<0.001) was observed in the intervention compared to the non-intervention. Changes in immune cells were not significant in either group.
This feasibility study demonstrates that in overweight men with localized CaP, weight loss alters blood, and tissue biomarkers, as well as tumor gene expression. More research is needed to determine the biological and clinical significance of these findings.
已有多项生物学机制被提出，以解释肥胖在前列腺癌（CaP）进展中的作用，其中包括炎症和免疫改变。与体重健康的男性相比，超重和肥胖男性在前列腺切除术后更有可能出现 CaP 复发。肥胖与炎症和免疫失调有关；因此，减肥可能是减轻炎症和逆转这些免疫过程的一种途径。
本研究通过对接受前列腺切除术的男性进行综合体重管理计划，探讨通过有意减肥来逆转这些生物学机制的可能性。研究结果包括血液和组织生物标志物、微小肿瘤环境基因表达、炎症标志物和膳食炎症指数（DII）评分。
本研究纳入了 20 名超重男性，他们均接受了前列腺切除术。其中 15 名男性选择了干预组，5 名男性选择了非干预组。干预组在前列腺术前接受了全面的减肥计划，并在术后接受了体重维持计划。研究人员在干预前的诊断性活检和前列腺切除术后的样本中获取了前列腺组织样本。在基线、术前减肥后和研究结束后的体重维持后收集了血液样本和饮食记录。研究人员使用免疫组织化学和 NanoString 分析方法来分析组织样本，使用流式细胞术来评估循环免疫标志物，使用 Luminex 试剂盒来测量炎症标志物。
干预组在术前体重减轻了>5%。DII 评分在减肥干预期间从基线到术前（P=0.002）有所改善，且组间差异有统计学意义（P=0.02）。DII 评分与 IL-6 或 hsCRP 均无相关性。在干预组中，从活检到手术时，前列腺组织中 CXCL12、CXCR7 和 CXCR4（C-X-C 基序趋化因子配体/受体）和 Ki67 的表达减少（P=0.06），而同一时间内的血浆 CXCL12 增加（P=0.009）。与非干预组相比，干预组中观察到多个基因的下调（FDR<0.001）。两组的免疫细胞变化均不显著。
本可行性研究表明，在患有局限性 CaP 的超重男性中，减肥可改变血液和组织生物标志物以及肿瘤基因表达。需要进一步研究以确定这些发现的生物学和临床意义。
