Prediction of hepatocellular carcinoma prognosis and immunotherapeutic effects based on tryptophan metabolism-related genes

Abstract

Abstract Background L-tryptophan (Trp) metabolism involved in mediating tumour development and immune suppression. However, comprehensive analysis of the role of the Trp metabolism pathway is still a challenge. Methods We downloaded Trp metabolism-related genes’ expression data from different public databases, including TCGA, Gene Expression Omnibus (GEO) and Hepatocellular Carcinoma Database (HCCDB). And we identified two metabolic phenotypes using the ConsensusClusterPlus package. Univariate regression analysis and lasso Cox regression analysis were used to establish a risk model. CIBERSORT and Tracking of Indels by DEcomposition (TIDE) analyses were adopted to assess the infiltration abundance of immune cells and tumour immune escape. Results We identified two metabolic phenotypes, and patients in Cluster 2 (C2) had a better prognosis than those in Cluster 1 (C1). The distribution of clinical features between the metabolic phenotypes showed that patients in C1 tended to have higher T stage, stage, grade, and death probability than those of patients in C2. Additionally, we screened 739 differentially expressed genes (DEGs) between the C1 and C2. We generated a ten-gene risk model based on the DEGs, and the area under the curve (AUC) values of the risk model for predicting overall survival. Patients in the low-risk subgroup tended to have a significantly longer overall survival than that of those in the high-risk group. Moreover, univariate analysis indicated that the risk model was significantly correlated with overall survival. Multivariate analysis showed that the risk model remained an independent risk factor in hepatocellular carcinoma (p < 0.0001). Conclusions We identified two metabolic phenotypes based on genes of the Trp metabolism pathway, and we established a risk model that could be used for predicting prognosis and guiding immunotherapy in patients with hepatocellular carcinoma.

Keywords

• HCC
• Trp metabolism
• Metabolic phenotype
• Risk model
• Prognosis
• Immune escape