*Section of Biosurgery and Surgical Technology, Department of Surgery and Cancer, Faculty of Medicine, St Mary's Hospital, Imperial College London †Section of Computational and Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London ‡Centre for Pathology, Department of Medicine, Faculty of Medicine, St Mary's Hospital, Imperial College London, London, United Kingdom.
Ann Surg. 2014 Jun;259(6):1138-49. doi: 10.1097/SLA.0b013e31829d5c45.
To develop novel metabolite-based models for diagnosis and staging in colorectal cancer (CRC) using high-resolution magic angle spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy.
Previous studies have demonstrated that cancer cells harbor unique metabolic characteristics relative to healthy counterparts. This study sought to characterize metabolic properties in CRC using HR-MAS NMR spectroscopy.
Between November 2010 and January 2012, 44 consecutive patients with confirmed CRC were recruited to a prospective observational study. Fresh tissue samples were obtained from center of tumor and 5 cm from tumor margin from surgical resection specimens. Samples were run in duplicate where tissue volume permitted to compensate for anticipated sample heterogeneity. Samples were subjected to HR-MAS NMR spectroscopic profiling and acquired spectral data were imported into SIMCA and MATLAB statistical software packages for unsupervised and supervised multivariate analysis.
A total of 171 spectra were acquired (center of tumor, n = 88; 5 cm from tumor margin, n = 83). Cancer tissue contained significantly increased levels of lactate (P < 0.005), taurine (P < 0.005), and isoglutamine (P < 0.005) and decreased levels of lipids/triglycerides (P < 0.005) relative to healthy mucosa (R2Y = 0.94; Q2Y = 0.72; area under the curve, 0.98). Colon cancer samples (n = 49) contained higher levels of acetate (P < 0.005) and arginine (P < 0.005) and lower levels of lactate (P < 0.005) relative to rectal cancer samples (n = 39). In addition unique metabolic profiles were observed for tumors of differing T-stage.
HR-MAS NMR profiling demonstrates cancer-specific metabolic signatures in CRC and reveals metabolic differences between colonic and rectal cancers. In addition, this approach reveals that tumor metabolism undergoes modification during local tumor advancement, offering potential in future staging and therapeutic approaches.
利用高分辨率魔角旋转核磁共振（HR-MAS NMR）光谱技术，为结直肠癌（CRC）的诊断和分期开发新的代谢物模型。
先前的研究表明，癌细胞相对于健康细胞具有独特的代谢特征。本研究旨在利用 HR-MAS NMR 光谱技术来描述 CRC 中的代谢特性。
2010 年 11 月至 2012 年 1 月，连续招募了 44 例确诊为 CRC 的患者进行前瞻性观察研究。从手术切除标本的肿瘤中心和肿瘤边缘 5cm 处获取新鲜组织样本。如果组织体积允许，将样本进行重复测试，以补偿预期的样本异质性。对样本进行 HR-MAS NMR 光谱分析，并将获得的光谱数据导入 SIMCA 和 MATLAB 统计软件包进行无监督和有监督的多元分析。
共采集了 171 个光谱（肿瘤中心，n=88；肿瘤边缘 5cm 处，n=83）。与健康黏膜相比，癌组织中乳酸盐（P<0.005）、牛磺酸（P<0.005）和异谷氨酰胺（P<0.005）水平显著升高，脂质/三酰甘油（P<0.005）水平显著降低（R2Y=0.94；Q2Y=0.72；曲线下面积，0.98）。与直肠肿瘤样本（n=39）相比，结肠肿瘤样本（n=49）中乙酸盐（P<0.005）和精氨酸（P<0.005）水平更高，乳酸盐（P<0.005）水平更低。此外，还观察到不同 T 分期的肿瘤具有独特的代谢谱。
HR-MAS NMR 分析显示 CRC 中存在癌症特异性代谢特征，并揭示了结直肠癌和直肠肿瘤之间的代谢差异。此外，这种方法表明肿瘤代谢在局部肿瘤进展过程中发生了改变，为未来的分期和治疗方法提供了潜力。
