Department of Public Health Sciences, University of Chicago Biological Sciences, 5841 S. Maryland Ave. MC2000, 60637, Chicago, IL, USA.
Institute for Population and Precision Health, University of Chicago, Chicago, IL, USA.
BMC Cancer. 2023 Feb 23;23(1):183. doi: 10.1186/s12885-023-10656-1.
Breast cancer survivors face long-term sequelae compared to the general population, suggesting altered metabolic profiles after breast cancer. We used metabolomics approaches to investigate the metabolic differences between breast cancer patients and women in the general population, aiming to elaborate metabolic changes among breast cancer patients and identify potential targets for clinical interventions to mitigate long-term sequelae.
Serum samples were retrieved from 125 breast cancer cases recruited from the Chicago Multiethnic Epidemiologic Breast Cancer Cohort (ChiMEC), and 125 healthy controls selected from Chicago Multiethnic Prevention and Surveillance Study (COMPASS). We used liquid chromatography-high resolution mass spectrometry to obtain untargeted metabolic profiles and partial least squares discriminant analysis (PLS-DA) combined with fold change to select metabolic features associated with breast cancer. Pathway analyses were conducted using Mummichog to identify differentially enriched metabolic pathways among cancer patients. As potential confounders we included age, marital status, tobacco smoking, alcohol drinking, type 2 diabetes, and area deprivation index in our model. Random effects of residence for intercept was also included in the model. We further conducted subgroup analysis by treatment timing (chemotherapy/radiotherapy/surgery), lymph node status, and cancer stages.
The entire study participants were African American. The average ages were 57.1 for cases and 58.0 for controls. We extracted 15,829 features in total, among which 507 features were eventually selected by our criteria. Pathway enrichment analysis of these 507 features identified three differentially enriched metabolic pathways related to prostaglandin, leukotriene, and glycerophospholipid. The three pathways demonstrated inconsistent patterns. Metabolic features in the prostaglandin and leukotriene pathways exhibited increased abundances among cancer patients. In contrast, metabolic intensity in the glycerolphospholipid pathway was deregulated among cancer patients. Subgroup analysis yielded consistent results. However, changes in these pathways were strengthened when only using cases with positive lymph nodes, and attenuated when only using cases with stage I disease.
Breast cancer in African American women is associated with increase in serum metabolites involved in prostaglandin and leukotriene pathways, but with decrease in serum metabolites in glycerolphospholipid pathway. Positive lymph nodes and advanced cancer stage may strengthen changes in these pathways.
与普通人群相比，乳腺癌幸存者面临长期的后遗症，这表明乳腺癌后代谢谱发生了改变。我们使用代谢组学方法研究了乳腺癌患者和普通人群之间的代谢差异，旨在阐述乳腺癌患者的代谢变化，并确定潜在的临床干预靶点，以减轻长期后遗症。
从芝加哥多民族癌症队列（ChiMEC）招募的 125 例乳腺癌患者和从芝加哥多民族预防和监测研究（COMPASS）中选择的 125 例健康对照者中提取血清样本。我们使用液相色谱-高分辨质谱法获得非靶向代谢谱，并结合偏最小二乘判别分析（PLS-DA）和倍数变化来选择与乳腺癌相关的代谢特征。使用 Mummichog 进行途径分析，以确定癌症患者中差异富集的代谢途径。作为潜在的混杂因素，我们在模型中包括年龄、婚姻状况、吸烟、饮酒、2 型糖尿病和地区剥夺指数。模型中还包括截距的居住的随机效应。我们还根据治疗时机（化疗/放疗/手术）、淋巴结状态和癌症分期进行了亚组分析。
整个研究参与者均为非裔美国人。病例组的平均年龄为 57.1 岁，对照组为 58.0 岁。我们总共提取了 15829 个特征，其中 507 个特征最终通过我们的标准筛选。对这 507 个特征的途径富集分析确定了与前列腺素、白三烯和甘油磷脂相关的三个差异富集代谢途径。这三个途径表现出不一致的模式。癌症患者中前列腺素和白三烯途径的代谢特征表现出增加的丰度。相反，甘油磷脂途径的代谢强度在癌症患者中失调。亚组分析得到了一致的结果。然而，当仅使用阳性淋巴结的病例时，这些途径的变化得到了加强，而当仅使用 I 期疾病的病例时，这些变化则减弱。
非裔美国女性的乳腺癌与涉及前列腺素和白三烯途径的血清代谢物增加有关，但与甘油磷脂途径的血清代谢物减少有关。阳性淋巴结和晚期癌症阶段可能会增强这些途径的变化。
