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

Lipid metabolism has been associated with progression of various cancers. However, the underlying mechanisms of the impact of lipid metabolism-associated genes (LMAGs) on the tumor immune microenvironment have not been well-elucidated. This study aimed to determine the effects of lipid metabolism on the progression and development of hepatocellular carcinoma (HCC). Expression profiles and clinical data of 371 and 231 patients with HCC were obtained from the TCGA and Internal Cancer Genome Consortium (ICGC) databases, respectively. Using Cox regression and LASSO regression analyses, a prognostic risk model was constructed based on the LMAG data. The tumor mutation burden (TMB), immune cell infiltration levels, and immune response checkpoints of the identified risk groups were determined and compared. A total of two clusters were identified based on the LMAG expression, showing significant differences in tumor stage and immune cell infiltration. A prognostic risk model based on four LMAGs was constructed and proven to have a significant prognostic value. The 1-, 3-, and 5-year survival rates in the high-risk group were 62.2%, 20.5%, and 8.1%, respectively, whereas those in the low-risk group were 78.9%, 28.1%, and 13.5%, respectively. The survival differences between the two risk groups were likely associated with TP53 mutation status, TMB score, degree of immunocyte infiltration, and immune checkpoint level. Likewise, the expression level of every LMAG included in the model had the same effect on the overall survival and immune cell infiltration levels. More importantly, the prognostic value of the signature was verified in an independent ICGC cohort. Thus, the expression levels of LMAGs are closely related to the tumor microenvironment in HCC and may serve as promising biological indicators for prognosis and immune therapy in patients with HCC.

Automated summary

This study explores the impact of lipid metabolism on the progression and development of hepatocellular carcinoma (HCC) and reveals the important role of lipid metabolism-associated genes (LMAGs) in the tumor immune microenvironment. By constructing a prognostic risk model, the researchers discovered significant differences in tumor stage and immune cell infiltration based on LMAG expression. Furthermore, the model showed significant prognostic value and the LMAGs may serve as promising biological indicators for prognosis and immune therapy in patients with HCC.