Combined analysis of metabolomics and transcriptomics reveals new indicators for the diagnosis and prognosis of colorectal cancer

Introduction
Abnormal cellular metabolism is one of the characteristics of tumour cells. However, the differences in the global metabolomics between normal and tumour tissues remain unclear. In this study, we have proposed a diagnostic and prognostic model for colorectal cancer (CRC) based on metabolomics and genomics.

Material and methods
Metabolomics data of CRC patients was obtained from the MetaboLights repository, and identified the characteristic metabolites of CRC cells through orthogonal partial least squares discriminant analysis (OPLS-DA). Then we performed differential analysis of these metabolites between normal and tumour tissues. Subsequent enrichment analysis was used to analyse the signalling pathways related to the differential metabolites. Finally, we combined metabolomics and genomics to construct a prognostic model, and detected the expression of key metabolites and genes in CRC cell lines by using ELISA and western blot.

Results
Based on the variable important in projection values of OPLS-DA, we identified 318 characteristic metabolites. By conducting differential analysis of these metabolites, we identified 30 downregulated and 42 upregulated metabolites in colorectal cancer. The combined analysis of enrichment pathways revealed that 5 pathways were enriched in both metabolomics and transcriptomics.

Conclusions
We established a prognostic model through univariate Cox and least absolute shrinkage and selection operator regression, and then verified the excellent application value of the model for patient prognosis through receiver operating characteristic curves and survival analysis. Finally, ELISA and western blot experiments showed that compared with normal colorectal epithelial cells, the levels of estradiol and formimidoyltransferase cyclodeaminase proteins were increased, while the levels of methionine and SLC5A1 proteins were decreased in CRC cells.