Rapid Diagnosis and Staging of Colorectal Cancer via High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance (HR-MAS NMR) Spectroscopy of Intact Tissue Biopsies

Abstract

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.