Choi Ji Soo, Baek Hyeon-Man, Kim Suhkmann, Kim Min Jung, Youk Ji Hyun, Moon Hee Jung, Kim Eun-Kyung, Nam Youn Ki
Department of Radiology, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Korea ; Department of Radiology, Samsung Medical Center, Seoul, Korea.
Division of Magnetic Resonance, Korea Basic Science Institute, Chungbuk, Korea ; Department of Bio-Analytical Science, University of Science and Technology, Daejeon, Korea.
PLoS One. 2013 Dec 19;8(12):e83866. doi: 10.1371/journal.pone.0083866. eCollection 2013.
The purpose of this study was to determine whether metabolic profiling of core needle biopsy (CNB) samples using high-resolution magic angle spinning (HR-MAS) magnetic resonance spectroscopy (MRS) could be used for predicting pathologic response to neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer. After institutional review board approval and informed consent were obtained, CNB tissue samples were collected from 37 malignant lesions in 37 patients before NAC treatment. The metabolic profiling of CNB samples were performed by HR-MAS MRS. Metabolic profiles were compared according to pathologic response to NAC using the Mann-Whitney test. Multivariate analysis was performed with orthogonal projections to latent structure-discriminant analysis (OPLS-DA). Various metabolites including choline-containing compounds were identified and quantified by HR-MAS MRS in all 37 breast cancer tissue samples obtained by CNB. In univariate analysis, the metabolite concentrations and metabolic ratios of CNB samples obtained with HR-MAS MRS were not significantly different between different pathologic response groups. However, there was a trend of lower levels of phosphocholine/creatine ratio and choline-containing metabolite concentrations in the pathologic complete response group compared to the non-pathologic complete response group. In multivariate analysis, the OPLS-DA models built with HR-MAS MR metabolic profiles showed visible discrimination between the pathologic response groups. This study showed OPLS-DA multivariate analysis using metabolic profiles of pretreatment CNB samples assessed by HR- MAS MRS may be used to predict pathologic response before NAC, although we did not identify the metabolite showing statistical significance in univariate analysis. Therefore, our preliminary results raise the necessity of further study on HR-MAS MR metabolic profiling of CNB samples for a large number of cancers.
本研究的目的是确定使用高分辨率魔角旋转（HR-MAS）磁共振波谱（MRS）对粗针穿刺活检（CNB）样本进行代谢谱分析是否可用于预测局部晚期乳腺癌患者对新辅助化疗（NAC）的病理反应。在获得机构审查委员会批准和知情同意后，在NAC治疗前从37例患者的37个恶性病变中采集CNB组织样本。通过HR-MAS MRS对CNB样本进行代谢谱分析。使用曼-惠特尼检验根据对NAC的病理反应比较代谢谱。采用正交投影到潜在结构判别分析（OPLS-DA）进行多变量分析。通过HR-MAS MRS在通过CNB获得的所有37个乳腺癌组织样本中鉴定并定量了包括含胆碱化合物在内的各种代谢物。在单变量分析中，不同病理反应组之间通过HR-MAS MRS获得的CNB样本的代谢物浓度和代谢比率没有显著差异。然而，与非病理完全缓解组相比，病理完全缓解组中的磷酸胆碱/肌酸比率和含胆碱代谢物浓度有降低的趋势。在多变量分析中，用HR-MR代谢谱建立的OPLS-DA模型在病理反应组之间显示出明显的区分。本研究表明，使用HR-MAS MRS评估的预处理CNB样本的代谢谱进行OPLS-DA多变量分析可用于预测NAC前的病理反应，尽管我们在单变量分析中未发现具有统计学意义的代谢物。因此，我们的初步结果提出了对大量癌症的CNB样本进行HR-MAS MR代谢谱分析进一步研究的必要性。
