Identification of a glycolysis-related gene signature for predicting prognosis in patients with hepatocellular carcinoma

Abstract

Background Hepatocellular carcinoma (HCC) is the most common primary liver cancer in the world. Although great advances in HCC diagnosis and treatment have been achieved, due to the complicated mechanisms in tumor development and progression, the prognosis of HCC is still dismal. Recent studies have revealed that the Warburg effect is related to the development, progression and treatment of various cancers; however, there have been a few explorations of the relationship between glycolysis and HCC prognosis. Methods mRNA expression profiling was downloaded from public databases. Gene set enrichment analysis (GSEA) was used to explore glycolysis-related genes (GRGs), and the LASSO method and Cox regression analysis were used to identify GRGs related to HCC prognosis and to construct predictive models associated with overall survival (OS) and disease-free survival (DFS). The relationship between the predictive model and the tumor mutation burden (TMB) and tumor immune microenvironment (TIME) was explored. Finally, real-time PCR was used to validate the expression levels of the GRGs in clinical samples and different cell lines. Results Five GRGs (ABCB6, ANKZF1, B3GAT3, KIF20A and STC2) were identified and used to construct gene signatures to predict HCC OS and DFS. Using the median value, HCC patients were divided into low- and high-risk groups. Patients in the high-risk group had worse OS/DFS than those in the low-risk group, were related to higher TMB and were associated with a higher rate of CD4+ memory T cells resting and CD4+ memory T cells activated. Finally, real-time PCR suggested that the five GRGs were all dysregulated in HCC samples compared to adjacent normal samples. Conclusions We identified five GRGs associated with HCC prognosis and constructed two GRGs-related gene signatures to predict HCC OS and DFS. The findings in this study may contribute to the prediction of prognosis and promote HCC treatment.

Transcriptome and pan-cancer system analysis identify PM2.5-induced stanniocalcin 2 as a potential prognostic and immunological biomarker for cancers

“…Our study supported the above findings that the mutation types of STC2 in HNSC showed both missense and deletion mutations, and the percentage of missense mutations was relatively high. Some studies have found a close relationship between STC2 mutations and the onset and prognosis of liver cancer, especially in terms of overall survival and disease-free survival of patients (Kong et al, 2022). We found two types of mutations and amplifications of STC2 in liver cancer, with missense mutations as the predominant type, which confirmed the role of STC2 mutation in liver cancer.…”

Tumor Mutational Burden for Predicting Prognosis and Therapy Outcome of Hepatocellular Carcinoma

“…Other specific signatures that have been correlated to TMB, worse overall survival, and disease-free survival are glycolysis-related genes (GRGs) signatures [ 144 ] or piroptosis-related gene mutations [ 145 ]. Additionally, aberrant expressions of RNA terminal phosphate cyclase like 1 (RCL1) [ 146 ] and variation of mRNA expression-based stemness (mRNAsi) index [ 147 ] have been correlated with TMB and modification in overall survival.…”

Multimodal Integrative Genomics and Pathology Analyses in Neoadjuvant Nivolumab Treatment for Intermediate and Locally Advanced Hepatocellular Carcinoma

“…There was a relative shift from resting to activated CD4 memory T cells in the responsive cases, but a trend of reversed shift from activated to resting CD4 memory T cells in the nonresponsive cases. In a previous study, both CD4 memory resting and activated T cells were found to be associated with HCC patients with poorer prognosis [38]. As memory CD4 T cells typically represent the T-cell subsets produced during a primary immunogenic challenge and are persistent to generate a recall response to secondary challenge [39], whether the shift between the two activation statuses of CD4 memory T cells determines the physiologic responsiveness to nivolumab of HCC needs further investigation.…”