Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
NMR Biomed. 2012 Nov;25(11):1271-9. doi: 10.1002/nbm.2798. Epub 2012 Mar 8.
Breast cancer is a heterogeneous disease with a variable prognosis. Clinical factors provide some information about the prognosis of patients with breast cancer; however, there is a need for additional information to stratify patients for improved and more individualized treatment. The aim of this study was to examine the relationship between the metabolite profiles of breast cancer tissue and 5-year survival. Biopsies from breast cancer patients (n=98) were excised during surgery and analyzed by high-resolution magic angle spinning MRS. The data were analyzed by multivariate principal component analysis and partial least-squares discriminant analysis, and the findings of important metabolites were confirmed by spectral integration of the metabolite peaks. Predictions of 5-year survival using metabolite profiles were compared with predictions using clinical parameters. Based on the metabolite profiles, patients with estrogen receptor (ER)-positive breast cancer (n=71) were separated into two groups with significantly different survival rates (p=0.024). Higher levels of glycine and lactate were found to be associated with lower survival rates by both multivariate analyses and spectral integration, and are suggested as biomarkers for breast cancer prognosis. Similar metabolic differences were not observed for ER-negative patients, where survivors could not be separated from nonsurvivors. Predictions of 5-year survival of ER-positive patients using metabolite profiles gave better and more robust results than those using traditional clinical parameters. The results imply that the metabolic state of a tumor may provide additional information concerning breast cancer prognosis. Further studies should be conducted in order to evaluate the role of MR metabolomics as an additional clinical tool for determining the prognosis of patients with breast cancer.
乳腺癌是一种异质性疾病，预后各不相同。临床因素可提供一些关于乳腺癌患者预后的信息，但还需要其他信息来对患者进行分层，以实现更好的个体化治疗。本研究旨在探讨乳腺癌组织代谢谱与 5 年生存率的关系。在手术过程中切除了 98 例乳腺癌患者的活检组织，并通过高分辨率魔角旋转 MRS 进行分析。通过多元主成分分析和偏最小二乘判别分析对数据进行分析，并通过代谢物峰的光谱积分来确认重要代谢物的发现。使用代谢谱预测 5 年生存率的结果与使用临床参数的预测结果进行了比较。基于代谢谱，将雌激素受体（ER）阳性乳腺癌患者（n=71）分为两组，两组患者的生存率存在显著差异（p=0.024）。多元分析和光谱积分均表明，较高的甘氨酸和乳酸水平与较低的生存率相关，提示它们可作为乳腺癌预后的生物标志物。在 ER 阴性患者中未观察到类似的代谢差异，其中幸存者与非幸存者无法区分。使用代谢谱预测 ER 阳性患者的 5 年生存率的结果优于使用传统临床参数的结果。结果表明，肿瘤的代谢状态可能为乳腺癌的预后提供额外的信息。应进一步开展研究，以评估磁共振代谢组学作为确定乳腺癌患者预后的附加临床工具的作用。
