欧洲前瞻性肿瘤与营养调查中中前列腺癌诊断前十年血液代谢组的扰动

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

INTERNATIONAL JOURNAL OF CANCER

影响因子:4.7

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

DOI: 10.1002/ijc.35208

摘要

测量诊断前血液代谢物可能有助于识别前列腺癌的新风险因素。利用欧洲前瞻性肿瘤与营养调查（EPIC）研究中4387对匹配病例-对照的资料，我们研究了148种单一代谢物及三种既定代谢模式与前列腺癌风险的关联。代谢物通过液相色谱-质谱分析测定。采用多变量调整的条件逻辑回归估算每个对数代谢物浓度标准差增加的比值比（OR1SD），分析包括整体前列腺癌、晚期、高级别和侵袭性前列腺癌。采用Benjamini-Hochberg方法校正多重检验。总体而言，没有特定代谢物或代谢模式与整体、侵袭性或高级别前列腺癌显著相关（padj<0.05）。有六种磷脂酰胆碱（PCs）与在血液采集后10年内诊断的晚期前列腺癌呈负相关。代谢模式1（64个PC和三种羟基鞘氨醇）及模式2（两种酰基肉碱、谷氨酸、鸟氨酸和牛磺酸）也与晚期前列腺癌呈负相关；按随访时间分层分析在采血后10年内的诊断中观察到这些关联（OR1SD分别为0.80和0.76，95% CI分别为0.66-0.96和0.59-0.97），但随访时间延长后这些关联减弱（0.95和0.85，95% CI分别为0.82-1.10和0.67-1.06）。模式3（8个溶血磷脂酰胆碱）与前列腺癌死亡相关（0.82，95% CI 0.68-0.98）。我们的结果提示，血浆代谢物谱在检测到晚期疾病前十年内会随前列腺癌的存在而发生变化。

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.