Choi Ji Soo, Yoon Dahye, Koo Ja Seung, Kim Siwon, Park Vivian Youngjean, Kim Eun-Kyung, Kim Suhkmann, Kim Min Jung
Department of Radiology, Breast Cancer Center, Samsung Medical Center, Seoul, Korea.
Department of Chemistry, Center for Proteome Biophysics and Chemistry Institute for Functional Materials, Pusan National University, Busan, Korea.
Oncotarget. 2017 Jun 28;8(38):63405-63416. doi: 10.18632/oncotarget.18822. eCollection 2017 Sep 8.
Estrogen receptor (ER)-positive breast cancers overall have a good prognosis, however, some patients suffer relapses and do not respond to endocrine therapy. The purpose of this study was to determine whether there are any correlations between high-resolution magic angle spinning (HR-MAS) magnetic resonance spectroscopy (MRS) metabolic profiles of core needle biopsy (CNB) specimens and the molecular markers currently used in patients with ER-positive breast cancers. The metabolic profiling of CNB samples from 62 ER-positive cancers was performed by HR-MAS MRS. Metabolic profiles were compared according to human epidermal growth factor receptor 2 (HER2) and Ki-67 status, and luminal type, using the Mann-Whitney test. Multivariate analysis was performed with orthogonal projections to latent structure-discriminant analysis (OPLS-DA). In univariate analysis, the HER2-positive group was shown to have higher levels of glycine and glutamate, compared to the HER2-negative group (<0.01, and <0.01, respectively). The high Ki-67 group showed higher levels of glutamate than the low Ki-67 group without statistical significance. Luminal B cancers showed higher levels of glycine (=0.01) than luminal A cancers. In multivariate analysis, the OPLS-DA models built with HR-MAS MR metabolic profiles showed visible discrimination between the subgroups according to HER2 and Ki-67 status, and luminal type. This study showed that the metabolic profiles of CNB samples assessed by HR-MAS MRS can be used to detect potential prognostic biomarkers as well as to understand the difference in metabolic mechanism among subtypes of ER-positive breast cancer.
总体而言,雌激素受体(ER)阳性乳腺癌预后良好,然而,一些患者会复发且对内分泌治疗无反应。本研究的目的是确定粗针活检(CNB)标本的高分辨率魔角旋转(HR-MAS)磁共振波谱(MRS)代谢谱与目前用于ER阳性乳腺癌患者的分子标志物之间是否存在任何相关性。通过HR-MAS MRS对62例ER阳性癌症的CNB样本进行代谢谱分析。使用曼-惠特尼检验,根据人表皮生长因子受体2(HER2)和Ki-67状态以及管腔型比较代谢谱。采用正交投影到潜在结构判别分析(OPLS-DA)进行多变量分析。在单变量分析中,与HER2阴性组相比,HER2阳性组的甘氨酸和谷氨酸水平较高(分别<0.01和<0.01)。高Ki-67组的谷氨酸水平高于低Ki-67组,但无统计学意义。管腔B型癌症的甘氨酸水平高于管腔A型癌症(=0.01)。在多变量分析中,用HR-MAS MR代谢谱建立的OPLS-DA模型显示,根据HER2和Ki-67状态以及管腔型,各亚组之间有明显的区分。本研究表明,通过HR-MAS MRS评估的CNB样本的代谢谱可用于检测潜在的预后生物标志物,以及了解ER阳性乳腺癌各亚型之间代谢机制的差异。