Abstract :
Background: Previous studies have demonstrated that cancer cells harbor unique metabolic characteristics relative to healthy counterparts. The current study is a prospective ex-vivo HR-MAS NMR analysis of malignant colorectal cancer (CRC) tissue specimens and its corresponding benign tissues.
Objective: To assess the HR-MAS Spectroscope qualitatively & to analyze significant difference between the normal, benign and malignant intestinal mucosa.
Materials and Methods: Between November 2013and January 2016, 36 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. Typically, the sample was packed into a 4 mm ZrO2 rotor of 50 ?l capacity; a volume of 20?l of D2O having 0.03% TSP was used as a chemical shift reference. The sample-rotor-setup was then transferred into the HR-MAS NMR probe for analysis.
Results: A total of 36 spectra were acquired (center of tumor, n = 18; 5 cm from tumor margin, n = 18). The malignant clustering occurs due to increased Val (0.90ppm), Lac (1.34ppm), Ala(1.48ppm) levels of acetate (1.90ppm), glutamate (2.35ppm), taurine (3.23 ppm), choline containing compounds (3.20-3.22ppm), glycine (3.56ppm), lactate (4.12ppm) and ?-H of Leu, Ileu, Val, Lys, Ala (3.76-3.79ppm . In addition unique metabolic profiles were observed for tumors of differing T-stage. The information gathered from clustering in PCA had highly suggested that malignancy induces metabolic perturbations at cellular levels.
Conclusions: HR-MAS NMR profiling demonstrates cancer-specific metabolic signatures in CRC and reveals metabolic differences between benign and malignant tumors. In addition, this approach reveals that tumor metabolism undergoes modification during local tumor advancement, offering potential in future staging and therapeutic approaches.
Keyword :
Colorectal cancer (CRC)