Metabolomics Analysis Of Colorectal Cancer Based On GC-TOF-MS

[Background]The incidence and mortality rates of colorectal cancer (CRC) rank third and fifth respectively in cancer incidence and mortality rates in china, and have a gradual upward trend. Because the early symptoms are not obvious, lacking high sensitivity and specificity of serum markers, the majority of patients are diagnosed when is advanced and the treatment effect of surgery combined with radiotherapy and (or) chemotherapy has been becoming more and more difficult to meet expectations of patients. Therefore, it is necessary to deepen the understanding of CRC, in order to improve the treatment method and treatment effect. Metabolomics approach rising in recent years has found that metabolic pathway of nucleic acids, amino acids, fatty acids, carbohydrate, etc, are altered in malignant tumor tissues makes people have a further understanding to life activities of malignant tumor cells, which provides a new perspective for the study of tumor cells and shows great potential. [Objective]To explore the differences of metabolites among CRC cancer tissues, mucosa adjacent to cancer and normal mucosa by using metabolomics approach, and mapping differential metabolites with database to look for differential metabolic pathways. [Methods]According to the inclusion and exclusion criteria, we selected 25 patients diagnosed as CRC. Taking one portion of cancer tissue, adjacent mucosa and normal mucosa respectively from each patient. Samples were derivatized by N,O-Bis(trimethylsily) trifluoroacetamide first and then were detected by gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) analysis platform. Three kinds of tissues were compared with each other, and using principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) for data modeling. Finally we analyzed differential metabolites and mapped in the KEGG database to find the relevant metabolic pathways.[Results]Compared with normal mucosa,47 metabolites were found different in cancer tissues(p<0.05,q<0.05). After mapping in the KEGG database, we found galactose metabolism, pentose phosphate pathway, glutamate and glutamine metabolism, glutamate, alanine and aspartate metabolism changed significantly (p<0.05).Among 47 metabolites, D-fructose, D-galactose, mannose, glucose and D-galactonic acid are related to galactose metabolism; glucose, gluconic lactone, ribose and glucosaminic acid are related to pentose phosphate pathway; L-glutamate and L-glutamine are related to glutamate and glutamine metabolism; L-aspartate, L-glutamate, N-acetyl-L-aspartate and L-glutamine are related to glutamate, alanine and aspartate metabolism.Compared with normal mucosa,3 metabolites were found different in adjacent mucosa(p<0.05, q<0.05). After mapping in the KEGG database, we found galactose metabolism changed significantly (p<0.05). Among 3 metabolites, D-galactonic acid is related to galactose metabolism.Cancer tissues compared with adjacent mucosa we got 34 differential metabolites(p<0.05,q<0.05).After mapping in the KEGG database, we found galactose metabolism, pentose phosphate pathway, glutamate and glutamine metabolism, glutamate, alanine and aspartate metabolism changed significantly(p<0.05).Among 34 metabolites, D-fructose, D-galactose, mannose and glucose are related to galactose metabolism; gluconic lactone, glucose,6-phosphate glucose are related to pentose phosphate pathway; L-glutamate and L-glutamine are related to glutamate and glutamine metabolism; L-glutamate, N-acetyl-L-aspartate and L-glutamine are related to glutamate, alanine and aspartate metabolism.[Conclusions]Compared with normal mucosa, CRC cancer has a significant change in glucose metabolism and amino acid metabolism, which has important significance on the life activity of tumor cells. The metabolic differences between cancer tissues and normal mucosa are largest, while between adjacent mucosa and normal mucosa are smallest.