Identification and validation of a glycolysis-associated multiomics prognostic model for hepatocellular carcinoma

Abstract

Increased glycolysis has been reported as a major metabolic hallmark in many cancers, and is closely related to malignant behavior of tumors. However, the potential mechanism of glycolysis in hepatocellular carcinoma (HCC) and its prognostic value are not well understood. To address this, we investigated glycolysis-related gene expression data of patients with HCC from TCGA and ICGC. Patients were categorized into three different glycolysis-associated subgroups: Glycolysis-M, Glycolysis-H, and Glycolysis-L. We found that Glycolysis-H combined with Glycolysis-M (Glycolysis-H+M) subgroup was associated with poor overall survival and distinct cancer stem cell characteristics and immune infiltrate patterns. Additionally, multiomics-based analyses were conducted to evaluate genomic patterns of glycolysis subgroups, including their gene mutations, copy number variations, and RNA-sequencing data. Finally, a glycolysis-associated multiomics prognostic model (GMPM) consisting of 19 glycolysis-associated genes was developed. The capability of GMPM in categorizing patients with HCC into high- and low-risk groups was validated with independent HCC datasets. Finally, GMPM was confirmed as an independent risk factor for the prognosis of patients with HCC. We believe that our findings provide new insights into the mechanism of glycolysis and highlight the potential clinical value of GMPM in predicting the prognosis of patients with HCC.

N7-Methylguanosine Regulatory Genes Profoundly Affect the Prognosis, Progression, and Antitumor Immune Response of Hepatocellular Carcinoma

“…(AUC = 0.614) ( 25 ), and He et al (AUC = 0.705) ( 26 ). Although our model was not as accurate as the models of Deng et al (AUC = 0.757) ( 24 ) and Shen et al (AUC = 0.737) ( 27 ), the gene number of our signature is much smaller than their ones (5 vs. 19 and 10, respectively). Considering this fact, the calculation of the m7G risk score based on our model was more accessible, which was more beneficial for clinical practice.…”

“…Given that there have been some studies constructing signatures for HCC clinical assessments, we analyzed the similarities and differences between five existing signatures and ours ( 24 – 28 ) ( Table 3 ). It was not difficult to perceive that our novel m7G model exhibited several strengths.…”

Roles of cuproptosis-related gene DLAT in various cancers: a bioinformatic analysis and preliminary verification on pro-survival autophagy

“…La Rocca et al have observed reduced expressions of DLAT during T cell activation among patients with multiple sclerosis, another autoimmune disease ( La Rocca et al, 2017 ). Some current studies show that there exists an immune-stimulating tumor micro-environment among tumor cells with high glycolysis levels ( Deng et al, 2021 ; Jiang et al, 2021 ; Yang et al, 2021 ). These results preliminarily indicate the potential involvement of DLAT in the immune regulation of cancers.…”

KCNN4 Promotes the Stemness Potentials of Liver Cancer Stem Cells by Enhancing Glucose Metabolism

“…Strategies targeting CSC metabolic characteristics are regarded as new opportunities for cancer treatments. LCSCs are featured by both addicted glycolysis and sustained oxidative phosphorylation (OXPHOS), which means that glucose flows more to the glycolysis pathway, [9][10][11], while fatty acid and glutamate contribute to the enhanced OXPHOS [12,13]. Inhibiting glycolysis or fatty acid oxidation (FAO) by targeting specific regulatory molecules or key metabolic enzymes has been used to attenuate stem cell potentials [14,15].…”