Huang Jiaqi, Mondul Alison M, Weinstein Stephanie J, Karoly Edward D, Sampson Joshua N, Albanes Demetrius
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda, MD, USA.
Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA.
Oncotarget. 2017 Jul 11;8(28):45190-45199. doi: 10.18632/oncotarget.16775.
Two recent investigations found serum lipid and energy metabolites related to aggressive prostate cancer up to 20 years prior to diagnosis. To elucidate whether those metabolomic profiles represent etiologic or tumor biomarker signals, we prospectively examined serum metabolites of prostate cancer cases by size and extent of primary tumors in a nested case-control analysis in the ATBC Study cohort that compared cases diagnosed with T2 (n = 71), T3 (n = 51), or T4 (n = 15) disease to controls (n = 200). Time from fasting serum collection to diagnosis averaged 10 years (range 1-20). LC/MS-GC/MS identified 625 known compounds, and logistic regression estimated odds ratios (ORs) associated with one-standard deviation differences in log-metabolites. N-acetyl-3-methylhistidine, 3-methylhistidine and 2'-deoxyuridine were elevated in men with T2 cancers compared to controls (ORs = 1.38-1.79; 0.0002 ≤ p ≤ 0.01). By contrast, four lipid metabolites were inversely associated with T3 tumors: oleoyl-linoleoyl-glycerophosphoinositol (GPI), palmitoyl-linoleoyl-GPI, cholate, and inositol 1-phosphate (ORs = 0.49-0.60; 0.000017 ≤ p ≤ 0.003). Secondary bile acid lipids, sex steroids and caffeine-related xanthine metabolites were elevated, while two Krebs cycle metabolites were decreased, in men diagnosed with T4 cancers. Men with T2, T3, and T4 prostate cancer primaries exhibit qualitatively different metabolite profiles years in advance of diagnosis that may represent etiologic factors, molecular patterns reflective of distinct primary tumors, or a combination of both.
两项近期研究发现，在诊断出侵袭性前列腺癌的20年前，血清脂质和能量代谢物就与之相关。为了阐明这些代谢组学特征是代表病因信号还是肿瘤生物标志物信号，我们在ATBC研究队列的巢式病例对照分析中，根据原发性肿瘤的大小和范围，对前列腺癌病例的血清代谢物进行了前瞻性研究，该分析将诊断为T2期（n = 71）、T3期（n = 51）或T4期（n = 15）疾病的病例与对照组（n = 200）进行了比较。从空腹血清采集到诊断的时间平均为10年（范围1 - 20年）。液相色谱/质谱联用 - 气相色谱/质谱联用技术鉴定出625种已知化合物，逻辑回归估计了与对数代谢物一个标准差差异相关的优势比（OR）。与对照组相比，T2期癌症男性的N - 乙酰 - 3 - 甲基组氨酸、3 - 甲基组氨酸和2'-脱氧尿苷升高（OR = 1.38 - 1.79；0.0002 ≤ p ≤ 0.01）。相比之下，四种脂质代谢物与T3期肿瘤呈负相关：油酰 - 亚油酰 - 甘油磷酸肌醇（GPI）、棕榈酰 - 亚油酰 - GPI、胆酸盐和肌醇1 - 磷酸（OR = 0.49 - 0.60；0.000017 ≤ p ≤ 0.003）。在诊断为T4期癌症的男性中，次级胆汁酸脂质、性类固醇和咖啡因相关的黄嘌呤代谢物升高，而两种三羧酸循环代谢物降低。患有T2、T3和T4期前列腺癌原发肿瘤的男性在诊断前数年表现出质的不同的代谢物谱，这可能代表病因因素、反映不同原发性肿瘤的分子模式或两者的结合。
