在4387年前列腺癌诊断之前，血液代谢组的扰动持续了十年
Perturbations in the blood metabolome up to a decade before prostate cancer diagnosis in 4387 matched case-control sets from the European Prospective Investigation into Cancer and Nutrition
影响因子:4.70000
分区:医学2区 / 肿瘤学2区
发表日期:2025 Mar 01
作者:
Zoe S Grenville, Urwah Noor, Sabina Rinaldi, Marc J Gunter, Pietro Ferrari, Claudia Agnoli, Pilar Amiano, Alberto Catalano, María Dolores Chirlaque, Sofia Christakoudi, Marcela Guevara, Matthias Johansson, Rudolf Kaaks, Verena Katzke, Giovanna Masala, Anja Olsen, Keren Papier, Maria-Jose Sánchez, Matthias B Schulze, Anne Tjønneland, Tammy Y N Tong, Rosario Tumino, Elisabete Weiderpass, Raul Zamora-Ros, Timothy J Key, Karl Smith-Byrne, Julie A Schmidt, Ruth C Travis
摘要
测量诊断前血液代谢物可能有助于鉴定前列腺癌的新风险因素。利用来自4387个欧洲癌症和营养研究前瞻性研究的病例对照对的数据（EPIC）研究，我们研究了148种单独代谢产物和三种先前定义的代谢物模式与前列腺癌风险的关联。通过液相色谱 - 质谱法测量代谢产物。多变量调整后的有条件逻辑回归用于估计前列腺癌的日志代谢物浓度和代谢物模式（OR1SD）的每标准偏差增加的几率，总体上，高级，高级，积极进取。我们使用Benjamini-Hochberg方法纠正了多次测试。总体而言，特定的代谢产物或代谢产物模式与总体，侵略性或高级前列腺癌之间没有关联，而是通过多个测试阈值（PADJ <0.05）。六个磷脂酰胆碱（PC）与在收集血液后10年内或10年内诊断出的晚期前列腺癌成反比。代谢产物模式1（64个PC和3个羟基甲甲素蛋白）和2个（两种酰基肉碱，谷氨酸，鸟氨酸和牛磺酸）也与晚期前列腺癌成反比。当通过随访时间进行分层时，在招募后10年或10年内观察到这些关联（OR1SD 0.80，95％CI 0.66-0.96和0.76，0.59-0.97，但经过更长的随访后更弱（0.95，0.82-1.10和0.82-1.10和0.85，0.85，0.85，0.67-1.06）。模式3（8个溶液PC）与前列腺癌死亡有关（0.82，0.68-0.98）。我们的结果表明，在发现晚期疾病之前，血浆代谢产物谱的变化响应于前列腺癌的存在，直到十年。
Abstract
Measuring pre-diagnostic blood metabolites may help identify novel risk factors for prostate cancer. Using data from 4387 matched case-control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we investigated the associations of 148 individual metabolites and three previously defined metabolite patterns with prostate cancer risk. Metabolites were measured by liquid chromatography-mass spectrometry. Multivariable-adjusted conditional logistic regression was used to estimate the odds ratio per standard deviation increase in log metabolite concentration and metabolite patterns (OR1SD) for prostate cancer overall, and for advanced, high-grade, aggressive. We corrected for multiple testing using the Benjamini-Hochberg method. Overall, there were no associations between specific metabolites or metabolite patterns and overall, aggressive, or high-grade prostate cancer that passed the multiple testing threshold (padj <0.05). Six phosphatidylcholines (PCs) were inversely associated with advanced prostate cancer diagnosed at or within 10 years of blood collection. metabolite patterns 1 (64 PCs and three hydroxysphingomyelins) and 2 (two acylcarnitines, glutamate, ornithine, and taurine) were also inversely associated with advanced prostate cancer; when stratified by follow-up time, these associations were observed for diagnoses at or within 10 years of recruitment (OR1SD 0.80, 95% CI 0.66-0.96 and 0.76, 0.59-0.97, respectively) but were weaker after longer follow-up (0.95, 0.82-1.10 and 0.85, 0.67-1.06). Pattern 3 (8 lyso PCs) was associated with prostate cancer death (0.82, 0.68-0.98). Our results suggest that the plasma metabolite profile changes in response to the presence of prostate cancer up to a decade before detection of advanced-stage disease.