Identification of a Subtype of Hepatocellular Carcinoma with Poor Prognosis Based on Expression of Genes within the Glucose Metabolic Pathway

Abstract

Hepatocellular carcinoma (HCC) is the most prevalent primary cancer and a highly aggressive liver malignancy. Liver cancer cells reprogram their metabolism to meet their needs for rapid proliferation and tumor growth. In the present study, we investigated the alterations in the expression of the genes involved in glucose metabolic pathways as well as their association with the clinical stage and survival of HCC patients. We found that the expressions of around 30% of genes involved in the glucose metabolic pathway are consistently dysregulated with a predominant down-regulation in HCC tumors. Moreover, the differentially expressed genes are associated with an advanced clinical stage and a poor prognosis. More importantly, unsupervised clustering analysis with the differentially expressed genes that were also associated with overall survival (OS) revealed a subgroup of patients with a worse prognosis including reduced OS, disease specific survival, and recurrence-free survival. This aggressive subtype had significantly increased expression of stemness-related genes and down-regulated metabolic genes, as well as increased immune infiltrates that contribute to a poor prognosis. Collectively, this integrative study indicates that expressions of the glucose metabolic genes could be used as potential prognostic markers and/or therapeutic targets, which might be helpful in developing precise treatment for patients with HCC.

Development and validation of glycolysis‐related prognostic score for prediction of prognosis and chemosensitivity of pancreatic ductal adenocarcinoma

“…This study provided novel insights into the relationship between glycolysis and HCC. Another study 17 identified consistently dysregulated genes within the glucose metabolic pathways. On investigating the prognostic power of these genes on survival outcomes in HCC patients, two distinct molecular HCC subtypes were identified, with one subtype having significantly worse prognosis.…”

Identification and Characterization of Robust Hepatocellular Carcinoma Prognostic Subtypes Based on an Integrative Metabolite‐Protein Interaction Network

“…The associations between HCC poor prognosis and down‐regulation in multiple metabolism enzymes have also been recognized in previous studies. [ 13 , 43 , 44 ] However, the reason remains unclear. Here, we found that the down‐regulation of metabolism pathways was largely caused by DNA hyper‐methylation in various metabolic enzymes.…”

Identification of a five-immune gene model as an independent prognostic factor in hepatocellular carcinoma

“…Its morbidity and mortality continue to rise, causing more than 600,000 deaths annually [1,2]. The symptoms and signs of early HCC are hard to notice, making its diagnosis often delayed, which is partly related to the poor prognosis [3][4][5]. In addition, due to host variabilities, individuals with the same pathological stage may still have significant differences in the overall survival (OS) [6].…”