Background: This study aims to explore metabolic biomarkers and pathways in breast cancer prognosis. Methods: We performed a global post-radiotherapy (RT) urinary metabolomic analysis of 120 breast cancer patients: 60 progression-free (PF) patients as the reference and 60 with progressive disease (PD: recurrence, second primary, metastasis, or death). UPLC-MS/MS (Metabolon Inc.) identified 1742 biochemicals (1258 known and 484 unknown structures). Following normalization to osmolality, log transformation, and imputation of missing values, a Welch’s two-samplet-test was used to identify biochemicals and metabolic pathways that differed between PF and PD groups. Data analysis and visualization were performed with MetaboAnalyst. Results: Metabolic biomarkers and pathways that significantly differed between the PD and PF groups were the following: amino acid metabolism, including phenylalanine, tyrosine, and tryptophan biosynthesis (impact value (IV) = 1.00;p= 0.0007); histidine metabolism (IV = 0.60;p< 0.0001); and arginine and proline metabolism (IV = 0.70;p= 0.0035). Metabolites of carbohydrate metabolism, including glucose (p= 0.0197), sedoheptulose (p= 0.0115), and carboxymethyl lysine (p= 0.0098), were elevated in patients with PD. Gamma-glutamyl amino acids, myo-inositol, and oxidative stress biomarkers, including 7-Hydroxyindole Sulfate and sulfate, were elevated in patients who died (p≤ 0.05). Conclusions: Amino acid metabolism emerged as a key pathway in breast cancer progression, while carbohydrate and oxidative stress metabolites also showed potential utility as biomarkers for breast cancer progression. These findings demonstrate applications of metabolomics in identifying metabolic biomarkers and pathways as potential targets for predicting breast cancer progression.
背景：本研究旨在探索乳腺癌预后相关的代谢生物标志物及通路。方法：我们对120例乳腺癌患者进行了放疗后尿液代谢组学全局分析，其中60例无进展患者作为参照组，60例疾病进展患者（包括复发、第二原发癌、转移或死亡）作为进展组。采用UPLC-MS/MS技术（Metabolon公司）共鉴定出1742种生化物质（1258种已知结构，484种未知结构）。数据经渗透压归一化、对数转换及缺失值填补后，采用韦尔奇双样本t检验识别两组间差异显著的生化物质及代谢通路。数据分析与可视化通过MetaboAnalyst平台完成。结果：进展组与无进展组间存在显著差异的代谢生物标志物及通路包括：氨基酸代谢通路——苯丙氨酸、酪氨酸和色氨酸生物合成（影响值=1.00，p=0.0007）、组氨酸代谢（影响值=0.60，p<0.0001）以及精氨酸和脯氨酸代谢（影响值=0.70，p=0.0035）。进展组患者碳水化合物代谢产物水平升高，包括葡萄糖（p=0.0197）、景天庚酮糖（p=0.0115）和羧甲基赖氨酸（p=0.0098）。死亡患者中γ-谷氨酰氨基酸、肌醇及氧化应激生物标志物（7-羟基吲哚硫酸盐和硫酸盐）水平显著升高（p≤0.05）。结论：氨基酸代谢通路是乳腺癌进展的关键通路，碳水化合物及氧化应激代谢产物亦显示出作为乳腺癌进展生物标志物的潜在价值。本研究证实了代谢组学在识别代谢生物标志物及通路方面的应用价值，这些发现可为预测乳腺癌进展提供潜在靶点。
Metabolomic Profiling of Disease Progression Following Radiotherapy for Breast Cancer
肿瘤(癌症)患者之家