A novel prognostic signature for colorectal cancer based on seven-metabolic-related genes

Emerging studies have suggested that metabolic enzymes and transporters (METs) have a close relationship with cancer development. However, the prognostic value and the associated mechanisms of METs in colorectal cancer (CRC) remain unclear. In this study, our aim was to identify prognostic MET signature and elucidate the potential underlying mechanism of MET in regulating CRC process. A total of 326 differential expression of MET genes (DEMETs) were identified by Limma R package with data downloaded from TCGA and GEO databases. Univariate and multivariate Cox regressions identified GDPD3, AQP8, GPX3, HPGD, CKMT2, CPT2 and CLCA1 as a robust prognostic METs signature, followed by the construction of the risk score model and nomogram in predicting the prognosis of CRC patient. TIDE algorithm showed that CRC patients in low- and high-risk groups had different response to immunotherapy. Somatic processes were downloaded from the GDC database and found that MUC16, FAT4, BDP1, CMYA5, ZNF735, CENPE, SLITRK2, ZNF208, CFAP46 and ALDH1A2 were the top 10 mutated genes in both the high- and low-risk groups. Moreover, a pharmacological network including HPGD, 38 active compounds and 115 herbs was constructed. These findings enrich our understanding of the relationships among METs, immune, and CRC, and may provide novel ideas in the treatment of CRC patients.