Prognostic Significance and Immunometabolism Landscapes Analysis of a Novel Lipid Metabolism-Related Gene Signature in Extrahepatic Metastasis of Hepatocellular Carcinoma.

Background: With the progress of hepatocellular carcinoma (HCC) treatment methods, the incidence rate of extrahepatic metastasis (EHM) of HCC has increased, which has a significant impact on patient prognosis. Lipid metabolism reprogramming has emerged as an important feature of HCC. However, the prognostic potential of lipid metabolism-related genes in EHM of HCC has not been comprehensively studied. Methods: : Sixty-five metastasis-related differentially expressed genes (DEGs) were obtained from the GEO database. HCC patients in the TCGA database were used as the training cohort for hierarchical clustering, and specimens in the ICGC database were used as the validation cohort. Enrichment analysis was performed by GO, KEGG, and GSEA, and the validated lipid metabolism score methods were used to evaluate lipid metabolism levels. A LASSO regression model was applied to select prognostic genes and construct the LMRMS. The CIBERSORT algorithm and ssGSEA were used to estimate immune infiltration. qPCR and Western blotting were used to detect expression levels of the target genes. Results: : First, we obtained two metastasis risk subtypes. The high metastasis risk group had a high lipid metabolism score and poor survival prognosis. Enrichment analysis showed that there were significant differences in a variety of lipid metabolism and drug metabolism pathways between the two subtypes. We further established an LMRMS. Immune infiltration showed different immune landscapes between the two subtypes. The LMRMS can effectively predict overall survival (OS), lipid metabolism level, different immune landscapes, and immunotherapy response and was well verified in the validation cohort. In vitro experiments confirmed that gene expression in the LMRMS was closely related to lipid metabolism, which is worthy of further study. Conclusions: : We first studied the prognostic significance and immunometabolic landscape of lipid metabolism-related genes in EHM of HCC. We propose an LMRMS, which can provide vital guidance for early identification of high-risk EHM patients and individualized immunotherapy for patients with EHM of HCC.