Novel Prognostic Signatures of Hepatocellular Carcinoma Based on Metabolic Pathway Phenotypes

Hepatocellular carcinoma is a disastrous cancer with an aberrant metabolism. In this study, we aimed to assess the role of metabolism in the prognosis of hepatocellular carcinoma. Ten metabolism-related pathways were identified to classify the hepatocellular carcinoma into two clusters: Metabolism_H and Metabolism_L. Compared with Metabolism_L, patients in Metabolism_H had lower survival rates with more mutated TP53 genes and more immune infiltration. Moreover, risk scores for predicting overall survival based on eleven differentially expressed metabolic genes were developed by the least absolute shrinkage and selection operator (LASSO)-Cox regression model in The Cancer Genome Atlas (TCGA) dataset, which was validated in the International Cancer Genome Consortium (ICGC) dataset. The immunohistochemistry staining of liver cancer patient specimens also identified that the 11 genes were associated with the prognosis of liver cancer patients. Multivariate Cox regression analyses indicated that the differentially expressed metabolic gene-based risk score was also an independent prognostic factor for overall survival. Furthermore, the risk score (AUC = 0.767) outperformed other clinical variables in predicting overall survival. Therefore, the metabolism-related survival-predictor model may predict overall survival excellently for HCC patients.