Abstract
BackgroundRectal cancer is one of the most prevalent tumor types. Understanding the metabolic profile of rectal cancer is important for developing therapeutic approaches and molecular diagnosis.MethodsHere, we report a metabonomics profiling of tissue samples on a large cohort of human rectal cancer subjects (n = 127) and normal controls (n = 43) using 1H nuclear magnetic resonance (1H NMR) based metabonomics assay, which is a highly sensitive and non-destructive method for the biomarker identification in biological systems. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and orthogonal projection to latent structure with discriminant analysis (OPLS-DA) were applied to analyze the 1H-NMR profiling data to identify the distinguishing metabolites of rectal cancer.ResultsExcellent separation was obtained and distinguishing metabolites were observed among the different stages of rectal cancer tissues (stage I = 35; stage II = 37; stage III = 37 and stage IV = 18) and normal controls. A total of 38 differential metabolites were identified, 16 of which were closely correlated with the stage of rectal cancer. The up-regulation of 10 metabolites, including lactate, threonine, acetate, glutathione, uracil, succinate, serine, formate, lysine and tyrosine, were detected in the cancer tissues. On the other hand, 6 metabolites, including myo-inositol, taurine, phosphocreatine, creatine, betaine and dimethylglycine were decreased in cancer tissues. These modified metabolites revealed disturbance of energy, amino acids, ketone body and choline metabolism, which may be correlated with the progression of human rectal cancer.ConclusionOur findings firstly identify the distinguishing metabolites in different stages of rectal cancer tissues, indicating possibility of the attribution of metabolites disturbance to the progression of rectal cancer. The altered metabolites may be as potential biomarkers, which would provide a promising molecular diagnostic approach for clinical diagnosis of human rectal cancer. The role and underlying mechanism of metabolites in rectal cancer progression are worth being further investigated.
Highlights
Colorectal cancer (CRC) is the third most frequent malignancy and the fourth most common cause of cancer mortality worldwide [1]
These metabolites included lactate, threonine, acetate, glutathione, uracil, succinate, serine, formate, lysine, tyrosine, myo-inositol, taurine, phosphocreatine, creatine, betaine, dimethylglycine, which are known to be involved in multiple metabolic processes, especially in energy and amino acid metabolism [14,15]
The results showed an apparent separation between rectal cancer tissues and normal controls on the scores plot of first two principal components (PC) (Figure 2A)
Summary
Colorectal cancer (CRC) is the third most frequent malignancy and the fourth most common cause of cancer mortality worldwide [1]. Metabolomics is an emerging field of research downstream of transcriptomics, genomics, and proteomics, which mainly involves the multicomponent analysis of biological fluids, tissues and cell extracts. It is currently used as a model of research in many disciplines of medicine, including disease diagnosis [3,4], biomarker screening [5,6], nutritional intervention [7] and safety assessment of chemical [8,9]. The number of patient tissues in these studies was limited, which cannot provide accurate and comprehensive information of CRC metabolites. Understanding the metabolic profile of rectal cancer is important for developing therapeutic approaches and molecular diagnosis
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