Identification and validation of ADME genes as prognosis and therapy markers for hepatocellular carcinoma patients
Purpose: ADME genes are genes involved in drug absorption, distribution, metabolism, and excretion (ADME). Previous studies report that expression levels of ADME-related genes correlate with prognosis of hepatocellular carcinoma (HCC) patients. However, the role of ADME gene expression on HCC prognosis has not been fully explored. This study sought to construct a prediction model using ADME-related genes for prognosis of HCC. Methods: Transcriptome and clinical data were retrieved from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC), which were used as training and validation cohorts, respectively. A prediction model was constructed using univariate Cox regression and LASSO analysis. Patients were divided into high- and low-risk groups based on the median risk score. The predictive ability of the risk signature was estimated through bioinformatics analyses. Results: Six ADME-related genes (CYP2C9, ABCB6, ABCC5, ADH4, DHRS13, and SLCO2A1) were used to construct the prediction model with a good predictive ability. Univariate and multivariate Cox regression analyses showed the risk signature was an independent predictor of overall survival. A single-sample gene set enrichment analysis (ssGSEA) strategy showed a significant relationship between risk signature and immune status. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed differentially expressed genes in the high- and low-risk groups were enriched in biological process associated with metabolic and cell cycle pathways. Conclusion: A prediction model was constructed using six ADME-related genes for prediction of HCC prognosis. This signature can be used to improve HCC diagnosis, treatment, and prognosis in clinical use.