Development of a novel lipid metabolism-based risk score model in hepatocellular carcinoma patients

BMC Gastroenterol. 2021 Feb 12;21(1):68. doi: 10.1186/s12876-021-01638-3.

Abstract

Background: Liver cancer is one of the most common malignancies worldwide. HCC (hepatocellular carcinoma) is the predominant pathological type of liver cancer, accounting for approximately 75-85 % of all liver cancers. Lipid metabolic reprogramming has emerged as an important feature of HCC. However, the influence of lipid metabolism-related gene expression in HCC patient prognosis remains unknown. In this study, we performed a comprehensive analysis of HCC gene expression data from TCGA (The Cancer Genome Atlas) to acquire further insight into the role of lipid metabolism-related genes in HCC patient prognosis.

Methods: We analyzed the mRNA expression profiles of 424 HCC patients from the TCGA database. GSEA(Gene Set Enrichment Analysis) was performed to identify lipid metabolism-related gene sets associated with HCC. We performed univariate Cox regression and LASSO(least absolute shrinkage and selection operator) regression analyses to identify genes with prognostic value and develop a prognostic model, which was tested in a validation cohort. We performed Kaplan-Meier survival and ROC (receiver operating characteristic) analyses to evaluate the performance of the model.

Results: We identified three lipid metabolism-related genes (ME1, MED10, MED22) with prognostic value in HCC and used them to calculate a risk score for each HCC patient. High-risk HCC patients exhibited a significantly lower survival rate than low-risk patients. Multivariate Cox regression analysis revealed that the 3-gene signature was an independent prognostic factor in HCC. Furthermore, the signature provided a highly accurate prediction of HCC patient prognosis.

Conclusions: We identified three lipid-metabolism-related genes that are upregulated in HCC tissues and established a 3-gene signature-based risk model that can accurately predict HCC patient prognosis. Our findings support the strong links between lipid metabolism and HCC and may facilitate the development of new metabolism-targeted treatment approaches for HCC.

Keywords: Hepatocellular carcinoma; Lipid metabolism; Predicting model.

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Carcinoma, Hepatocellular* / genetics
  • Humans
  • Kaplan-Meier Estimate
  • Lipid Metabolism / genetics
  • Liver Neoplasms* / genetics
  • Mediator Complex
  • Risk Factors

Substances

  • Biomarkers, Tumor
  • MED10 protein, human
  • MED22 protein, human
  • Mediator Complex