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

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.

A Novel Risk Model Based on Lipid Metabolism-Associated Genes Predicts Prognosis and Indicates Immune Microenvironment in Breast Cancer

“…MED10 encodes the mediator of RNA polymerase II transcription subunit 10 (MED10), and previous studies have suggested that MED10 expression is a risk factor for multiple types of tumors ( Xu et al, 2018 ; Sahar et al, 2019 ; Wang et al, 2021 ). Xu et al (2018) and Wang et al (2021) demonstrated that MED10 is a critical prognostic gene in glioblastoma and hepatocellular carcinoma, respectively. The protein level of MED10 has also been shown to be upregulated in uterine leiomyoma compared to that in the adjacent myometrium ( Sahar et al, 2019 ).…”

Identification of lipid metabolism-associated genes as prognostic biomarkers based on the immune microenvironment in hepatocellular carcinoma

“…With respect to other tumors, MED7 underexpression was correlated with an increased risk of gastrointestinal stroma ( Koschubs et al, 2009 ), while in breast cancer, especially ER + luminal subtypes, MED7 was positively correlated with improved prognosis ( Joseph et al, 2018 ). Moreover, MED22 was found to be significantly correlated with prognosis of HCC ( Wang et al, 2021 ). With respect to TXNRD1, the fourth LMAG identified in the study, inhibiting the NRF2/TXNRD1 signaling axis has been demonstrated as an efficient approach to restrain HCC growth, and combination therapy with sorafenib and NRF2/TXNRD1 inhibitors may be a promising strategy for personalized HCC treatment ( Gao et al, 2020 ).…”

Screening for Lipid-Metabolism-Related Genes and Identifying the Diagnostic Potential of ANGPTL6 for HBV-Related Early-Stage Hepatocellular Carcinoma

“…The purpose of metabolic reprogramming is to provide large amounts of energy for the adaptive growth and proliferation of tumor cells [ 61 , 62 , 63 ]. Among them, lipid metabolic reprogramming is one of the key features of hepatocarcinogenesis and development [ 61 , 64 , 65 ]. The dysregulated expression of genes related to lipid metabolism is involved in the lipid metabolic reprogramming process [ 66 , 67 ].…”