Prognostic Score-based Clinical Factors and Metabolism-related Biomarkers for Predicting the Progression of Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is a common malignant tumor representing more than 90% of primary liver cancer. This study aimed to identify metabolism-related biomarkers with prognostic value by developing the novel prognostic score (PS) model. Transcriptomic profiles derived from TCGA and EBIArray databases were analyzed to identify differentially expressed genes (DEGs) in HCC tumor samples compared with normal samples. The overlapped genes between DEGs and metabolism-related genes (crucial genes) were screened and functionally analyzed. A novel PS model was constructed to identify optimal signature genes. Cox regression analysis was performed to identify independent clinical factors related to prognosis. Nomogram model was constructed to estimate the predictability of clinical factors. Finally, protein expression of crucial genes was explored in different cancer tissues and cell types from the Human Protein Atlas (HPA). We screened a total of 305 overlapped genes (differentially expressed metabolism-related genes). These genes were mainly involved in “oxidation reduction,” “steroid hormone biosynthesis,” “fatty acid metabolic process,” and “linoleic acid metabolism.” Furthermore, we screened ten optimal DEGs (CYP2C9, CYP3A4, and TKT, among others) by using the PS model. Two clinical factors of pathologic stage (P < .001, HR: 1.512 [1.219-1.875]) and PS status (P <.001, HR: 2.259 [1.522-3.354]) were independent prognostic predictors by cox regression analysis. Nomogram model showed a high predicted probability of overall survival time, and the AUC value was 0.837. The expression status of 7 proteins was frequently altered in normal or differential tumor tissues, such as liver cancer and stomach cancer samples.We have identified several metabolism-related biomarkers for prognosis prediction of HCC based on the PS model. Two clinical factors were independent prognostic predictors of pathologic stage and PS status (high/low risk). The prognosis prediction model described in this study is a useful and stable method for novel biomarker identification.