Identification of five lipotoxicity-related genes as prognostic markers for hepatocellular carcinoma based on transcriptomic analyses and experimental validation.
TL;DR
This work has identified a five-gene lipotoxicity-related signature that may facilitate prognostic stratification of patients with HCC and provide a basis for further investigation of lipotoxicity-related prognostic markers.
Abstract
Hepatocellular carcinoma (HCC) is associated with a dismal prognosis. Although lipotoxicity has been shown to promote disease progression through inflammation and oxidative stress, the prognostic value of lipotoxicity-related genes (LTXGs) in HCC remains insufficiently defined. Using public transcriptomic datasets, lipotoxicity-related candidate genes were identified, and prognostic genes were screened by univariate Cox proportional hazards regression, proportional hazards (PH) assumption testing, least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox regression analyses. A risk-score model was constructed, and a nomogram integrating the risk score and tumor stage was subsequently developed. Functional enrichment analysis, immune infiltration analysis, and reverse-transcription quantitative polymerase chain reaction (RT-qPCR) validation were also performed. Five prognostic genes (SLC2A2, LCAT, PPARGC1A, CDKN2B, and GLP1R) were identified. Gene set enrichment analysis revealed that 35 pathways were differentially enriched between the high- and low-risk groups. Immune infiltration analysis demonstrated significantly higher infiltration of M0 macrophages in the high-risk group. RT-qPCR validation in clinical specimens confirmed that the expression levels of PPARGC1A and SLC2A2 were markedly higher in control tissues than in HCC tissues. This five-gene lipotoxicity-related signature may facilitate prognostic stratification of patients with HCC and provide a basis for further investigation of lipotoxicity-related prognostic markers.