Moreover, discriminating metabolites involved in the different pathological stages of rectal cancer have not been investigated. However, the number of patient tissues in these studies was limited, which cannot provide accurate and comprehensive information of CRC metabolites. Until now, only several NMR-based studies using patient colorectal cancer tissues have been reported. It has some advantages over MS in metabolic application, including non-destructive analysis, the relative ease of sample preparation, the potential to identify a broad range of compounds and the capacity for the supply of structural information for unknown compounds. NMR has been used extensively since 1970s. Three powerful analytical techniques are commonly applied to assay and quantify metabolites, including liquid chromatography (LC) coupled with mass spectrometry (MS), gas chromatography MS (GC/MS) and nuclear magnetic resonance (NMR). It is currently used as a model of research in many disciplines of medicine, including disease diagnosis, biomarker screening, nutritional intervention and safety assessment of chemical. 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. Therefore, early and accurate diagnosis of rectal cancer is critical for patients’ survival and improving therapeutic options for different stages of rectal cancer. The reasons that result in late diagnosis and therapy as well as disappointingly low survival rate include ineffective screening tools and guidelines, cancer detection at an advanced stage, limited survival achieved with palliative chemotherapy alone for patients with metastatic or unresectable disease. Five-year survival rate of rectal cancer patients is 93.5% for stage I, 87.4% for stage II, 58.2% for stage III, and 8.1% for stage IV. Tumor stage has a great influence on survival and is defined by UICC TNM (International Union against Cancer, Tumor Node Metastases) classification. Although advanced methods of diagnosis such as computed tomography (CT), ultrasonography (US), magnetic resonance imaging (MRI), and treatments such as surgery, neoadjuvant chemotherapy and radiation therapy, have been employed over the last few decades, the overall survival rate of patients with rectal cancer has not improved markedly. Among CRC, 65% of CRC are rectal cancer, which is located in the lower end of the colon. The role and underlying mechanism of metabolites in rectal cancer progression are worth being further investigated.Ĭolorectal cancer (CRC) is the third most frequent malignancy and the fourth most common cause of cancer mortality worldwide. The altered metabolites may be as potential biomarkers, which would provide a promising molecular diagnostic approach for clinical diagnosis of human rectal cancer. Our 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. 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. On the other hand, 6 metabolites, including myo-inositol, taurine, phosphocreatine, creatine, betaine and dimethylglycine were decreased in cancer tissues. The up-regulation of 10 metabolites, including lactate, threonine, acetate, glutathione, uracil, succinate, serine, formate, lysine and tyrosine, were detected in the cancer tissues. A total of 38 differential metabolites were identified, 16 of which were closely correlated with the stage of rectal cancer. ResultsĮxcellent 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. 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. Here, 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. Understanding the metabolic profile of rectal cancer is important for developing therapeutic approaches and molecular diagnosis. Rectal cancer is one of the most prevalent tumor types.
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