Non-invasive fecal metabonomic detection of colorectal cancer

Abstract

Colorectal cancer (CRC) is a major cause of mortality in many developed countries. Effective screening strategies were called for to facilitate timely detection and to promote a better clinical outcome. In this study, the role of fecal metabonomics in the non-invasive detection of CRC was investigated. Gas chromatography/time-of-flight mass spectrometry (GC/TOFMS) was utilized for the metabolic profiling of feces obtained from 11 CRC patients and 10 healthy subjects. Concurrently, matched tumor and normal mucosae surgically excised from CRC patients were profiled. CRC patients were differentiated clearly from healthy subjects based on their fecal metabonomic profiles (orthogonal partial least squares discriminant analysis [OPLS-DA], 1 predictive and 3 Y-orthogonal components, R (2)X = 0.373, R (2)Y = 0.995, Q (2) [cumulative] = 0.215). The robustness of the OPLS-DA model was demonstrated by an area of 1 under the receiver operator characteristic curve. OPLS-DA revealed fecal marker metabolites (e.g., fructose, linoleic acid, and nicotinic acid) that provided novel insights into the tumorigenesis of CRC. Interestingly, a disparate set of CRC-related metabolic aberrations occurred at the tissue level, implying the contribution of processes beyond the direct shedding of tumor cells to the fecal metabotype. In summary, this work established proof-of-principle for GC/TOFMS-based fecal metabonomic detection of CRC and offered new perspectives on the underlying mechanisms.

Keywords: colorectal cancer; feces; gas chromatography/time-of-flight mass spectrometry; metabolic profiling; metabolomics; metabonomics.

Figure 1. Fecal metabonomic profile of CRC patients and healthy subjects. (A) Typical GC/TOFMS chromatograms of fecal specimens from a CRC patient and a healthy subject (Hl). (B) PCA model 2 differentiating CRC patients from healthy subjects (Hl). (C) OPLS-DA model 2 differentiating CRC patients from healthy subjects (Hl). (D) Validation plot of OPLS-DA model 2.

Figure 2. Tissue metabonomic profile of tumor tissue and matched normal mucosae. (A) PCA scores plot discriminating CRC tumor (T) from matched normal mucosae (M). (B) OPLS-DA scores plot discriminating CRC tumor (T) from matched normal mucosae (M). (C) Validation plot of OPLS-DA model.