Background: High-risk prostate cancer is often treated with combined androgen deprivation therapy (ADT) and radiotherapy (RT). Blood biomarkers may enable treatments to be tailored to individual patients. Metabolomics, the study of small-molecule alterations in blood, is promising, and lipids are emerging as potential markers of poor prognosis. This study aims to investigate metabolic changes during prostate cancer treatment and their correlation to disease outcome.Methods: This study included 136 blood plasma samples from 35 patients with high-risk prostate cancer treated with RT and ADT, recruited from the Uppsala/Umeå Comprehensive Cancer Consortium (U-CAN) project. Blood samples were collected before, during, and after treatment and analyzed at Metabolon Inc. (Durham, NC, USA). To study differences in metabolic levels during treatment, three different sampling time points were considered: before ADT, in-between ADT and RT, and after RT. Both multivariate (orthogonal projections to latent structures, OPLS) and univariate analyses were performed, where statistical significance in combination with a large fold change was considered indicative of a substantial change.Results: Significant changes in metabolite levels were observed. Many of the significant metabolites for the whole course of treatment were also significant during ADT but not during RT, indicating that changes during ADT dominated the overall treatment. Changes were found to be especially common in steroids and fatty acids. Multivariate analysis revealed significant differences in metabolites between relapsing and non-relapsing patients. Among the significant metabolites were cholesterol and epiandrosterone.Conclusions: Metabolomics can identify biomarkers for prostate cancer treatment response and relapse. Further studies are needed to identify patterns and individual metabolites to personalize treatment strategies for prostate cancer.
背景：高危前列腺癌通常采用雄激素剥夺疗法（ADT）联合放射治疗（RT）进行治疗。血液生物标志物可能有助于为患者制定个体化治疗方案。代谢组学作为研究血液中小分子变化的方法，展现出良好前景，其中脂质类物质正逐渐成为不良预后的潜在标志物。本研究旨在探讨前列腺癌治疗期间的代谢变化及其与疾病结局的相关性。 方法：本研究纳入来自乌普萨拉/于默奥综合癌症联盟（U-CAN）项目的35例接受RT和ADT治疗的高危前列腺癌患者，共136份血浆样本。血液样本在治疗前、治疗期间及治疗后采集，并由美国北卡罗来纳州达勒姆市的Metabolon公司进行分析。为研究治疗期间代谢水平差异，设定三个采样时间点：ADT前、ADT与RT之间、RT后。研究采用多变量分析（正交偏最小二乘法，OPLS）和单变量分析，将统计学显著性与较大倍数变化结合作为显著变化的判定标准。 结果：观察到代谢物水平发生显著变化。在整个治疗过程中具有显著变化的代谢物中，多数在ADT期间同样显著，而在RT期间不显著，表明ADT期间的变化主导了整个治疗过程。研究发现类固醇和脂肪酸类物质的变化尤为常见。多变量分析显示复发与非复发患者的代谢物存在显著差异，其中胆固醇和表雄酮属于显著差异代谢物。 结论：代谢组学能够识别前列腺癌治疗反应及复发的生物标志物。未来需要进一步研究以明确代谢模式及特定代谢物，从而为前列腺癌制定个体化治疗策略。
Metabolomic Insights into Prostate Cancer Treatment and Relapse
肿瘤(癌症)患者之家