Reza Mirnezami1, Beatriz Jiménez, Jia V Li, James M Kinross, Kirill Veselkov, Robert D Goldin, Elaine Holmes, Jeremy K Nicholson, Ara Darzi. 1. *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.
Abstract
OBJECTIVE: 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. BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
OBJECTIVE: 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. BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Christopher Dietz; Felix Ehret; Francesco Palmas; Lindsey A Vandergrift; Yanni Jiang; Vanessa Schmitt; Vera Dufner; Piet Habbel; Johannes Nowak; Leo L Cheng Journal: NMR Biomed Date: 2017-09-15 Impact factor: 4.044
Authors: Alan S Wang; Alessia Lodi; Lee B Rivera; Jose L Izquierdo-Garcia; Matthew A Firpo; Sean J Mulvihill; Margaret A Tempero; Gabriele Bergers; Sabrina M Ronen Journal: NMR Biomed Date: 2014-09-09 Impact factor: 4.044