Metabolic characterization of primary human colorectal cancers using high resolution magic angle spinning 1H magnetic resonance spectroscopy

Abstract

Colorectal cancer is one of the most frequent and most lethal forms of cancer in the western world. The aim of this study is to characterize by 1 H high resolution magic angle spinning NMR spectroscopy (HRMAS) the metabolic fingerprint of both tumoral and healthy tissue samples obtained from a cohort of patients affected by primary colorectal adenocarcinoma. By analyzing HRMAS data using multivariate statistical analysis (PLS-DA), the two types of tissues could be discriminated with a high level of confidence. The identification of the metabolites at the origin of this discrimination revealed that adenocarcinomas are richer in taurine, glutamate, aspartate, and lactate whereas healthy tissues contain a higher amount of myo-inositol and b-glucose. The statistical model resulting from the PLS-DA analysis was subsequently used to perform a blind test on tumoral and healthy colon biopsies. The results of the classification showed that the HRMAS analysis has very high sensitivity and specificity.

Combining Information of Common Metabolites Reveals Global Differences between Colorectal Cancerous and Normal Tissues

“…The filtered solution was freeze-dried and the mass of the dried extract was measured and dissolved in 5 mM HEPES solution in D2O with 0.2 mM DSS, 0.5 mM NaN3 to the final volume-mass ratio C HSQC spectra were collected with 112 scans, 256 increments (TPPI), and 3sine decoupling. The spectral widths were 20 ppm for 1 H and 100 ppm for 13 C. The carbon carrier frequency was set at 55 ppm.…”

“…7 In this present study, we hypothesized that the metabolic profile in colorectal tissue would provide fingerprints of cancerous tissues that clearly differ from normal tissues. To test the hypothesis, we used two-dimensional 1 H- 13 C HSQC technique, 8,14 and profiled normal and cancerous tissue samples from 12 patients. We also compared our result with the traditional chemometric method based on one-dimensional 1 H spectra.…”

Metabolomic profile of the adrenal gland: from physiology to pathological conditions

“…To keep the rotation sidebands out of the spectral region of interest and to minimize sample degradation, all NMR experiments were conducted on samples spinning at 3502 Hz. For each sample, a one-dimensional (1D) proton spectrum using a Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence with presaturation of the water signal was acquired as reported previously (Piotto et al 2009). To eliminate signal losses due to B 1 inhomogeneity, the inter-pulse delay between the 1808 pulses of the CPMG pulse train was synchronized with the sample and set to 285 ms (Piotto et al 2001, Elbayed et al 2005.…”

Metabolomic NMR Fingerprinting to Identify and Predict Survival of Patients with Metastatic Colorectal Cancer

“…In recent years, metabolomic studies have provided a significant contribution to the detailed understanding of the biochemical network and pathways in oncology (11), highlighting the potential of metabolomic analyses of blood samples for the detection of cancers, including epithelial ovarian (12), leukemia (13), oral (14), breast (15,16), prostate (11), liver (17) as well as colorectal cancer (CRC; refs. [18][19][20][21][22][23][24][25]. CRC is the second most common cause of cancer-related deaths in Europe (26) and the third most common cause of cancerrelated deaths in the United States (27).…”

“…[18][19][20][21], nuclear magnetic resonance (NMR; refs. 22,23), or a combination of the two analytic tools (24).…”