Kataria Yachana, Wright Margaret, Deaton Ryan J, Rueter Erika Enk, Rybicki Benjamin A, Moser Ann B, Ananthanrayanan Vijayalakshmi, Gann Peter H
Department of Pathology, University of Illinois at Chicago, Chicago, Illinois.
Prostate. 2015 Feb;75(2):200-10. doi: 10.1002/pros.22905. Epub 2014 Oct 13.
Alpha-methylacyl-CoA racemase (AMACR) is an enzyme involved in fatty acid metabolism that is markedly over-expressed in virtually all prostate cancers (PCa), relative to benign tissue. One of AMACR's primary substrates, phytanic acid, is derived predominately from red meat and dairy product consumption. Epidemiological evidence suggests links between dairy/red meat intake, as well as phytanic acid levels, and elevated PCa risk. This study investigates the relationships among dietary intake, serum and tissue concentrations of phytanic acid, and AMACR expression (mRNA and protein) in the histologically benign human prostate.
Men undergoing radical prostatectomy for the treatment of localized disease provided a food frequency questionnaire (n = 68), fasting blood (n = 35), benign fresh frozen prostate tissue (n = 26), and formalin-fixed paraffin-embedded (FFPE) sections (n = 67). Serum and tissue phytanic acid concentrations were obtained by gas chromatography-mass spectrometry. We extracted RNA from epithelial cells using laser capture microdissection and quantified mRNA expression of AMACR and other genes involved in the peroxisomal phytanic acid metabolism pathway via qRT-PCR. Immunohistochemistry for AMACR was performed on FFPE sections and subsequently quantified via digital image analysis. Associations between diet, serum, and tissue phytanic acid levels, as well as AMACR and other gene expression levels were assessed by partial Spearman correlation coefficients.
High-fat dairy intake was the strongest predictor of circulating phytanic acid concentrations (r = 0.35, P = 0.04). Tissue phytanic acid concentrations were not associated with any dietary sources and were only weakly correlated with serum levels (r = 0.29, P = 0.15). AMACR gene expression was not associated with serum phytanic acid (r = 0.13, P = 0.47), prostatic phytanic acid concentrations (r = 0.03, P = 0.88), or AMACR protein expression (r = -0.16, P = 0.20).
Our data underscore the complexity of the relationship between AMACR and its substrates and do not support the unifying hypothesis that excess levels of dietary phytanic acid are responsible for both the overexpression of AMACR in prostate cancer and the potential association between PCa risk and intake of dairy foods and red meat.
α-甲基酰基辅酶A消旋酶（AMACR）是一种参与脂肪酸代谢的酶，相对于良性组织，它在几乎所有前列腺癌（PCa）中均显著过表达。AMACR的主要底物之一植烷酸主要来源于红肉和乳制品的摄入。流行病学证据表明，乳制品/红肉摄入以及植烷酸水平与PCa风险升高之间存在关联。本研究调查了组织学上为良性的人类前列腺中饮食摄入、血清和组织中植烷酸浓度以及AMACR表达（mRNA和蛋白质）之间的关系。
因局限性疾病接受根治性前列腺切除术的男性提供了食物频率问卷（n = 68）、空腹血样（n = 35）、良性新鲜冷冻前列腺组织（n = 26）以及福尔马林固定石蜡包埋（FFPE）切片（n = 67）。血清和组织中的植烷酸浓度通过气相色谱 - 质谱法测定。我们使用激光捕获显微切割从上皮细胞中提取RNA，并通过qRT - PCR定量AMACR以及参与过氧化物酶体植烷酸代谢途径的其他基因的mRNA表达。在FFPE切片上进行AMACR的免疫组织化学检测，随后通过数字图像分析进行定量。饮食、血清和组织中植烷酸水平以及AMACR和其他基因表达水平之间的关联通过偏Spearman相关系数进行评估。
高脂肪乳制品摄入是循环中植烷酸浓度的最强预测因素（r = 0.35，P = 0.04）。组织中的植烷酸浓度与任何饮食来源均无关联，且与血清水平仅呈弱相关（r = 0.29，P = 0.15）。AMACR基因表达与血清植烷酸（r = 0.13，P = 0.47）、前列腺植烷酸浓度（r = 0.03，P = 0.88）或AMACR蛋白表达（r = -0.16，P = 0.20）均无关联。
我们的数据强调了AMACR与其底物之间关系的复杂性，并不支持统一的假说，即饮食中植烷酸过量是导致前列腺癌中AMACR过表达以及PCa风险与乳制品和红肉摄入之间潜在关联的原因。
