LCLAT1 as a Potential Biomarker for Predicting Clinical Prognosis, Tumor Immunity, and Therapeutic Efficacy in Hepatocellular Carcinoma

ABSTRACT Lysocardiolipin acyltransferase 1 (LCLAT1) is a lipid acyltransferase that plays an important role in mitochondrial function maintenance and lipid metabolism. Nevertheless, there is scarce research regarding its involvement in tumors. This study sought to investigate the potential role of LCLAT1 in hepatocellular carcinoma (HCC). We obtained HCC expression profile data from The Cancer Genome Atlas and Gene Expression Omnibus databases; verified LCLAT1 expression in HCC by qRT–PCR, Western blotting, and immunohistochemical (IHC) staining; and analyzed the potential pathogenic mechanisms of LCLAT1 in HCC bioinformatically. The associations of the LCLAT1 expression level with HCC patient prognosis, immune escape, and treatment response were also explored using bioinformatics tools and IHC staining. LCLAT1 was significantly overexpressed in HCC cell lines and tissues, and its expression level was positively correlated with histologic grade, tumor status, fibrotic Ishak score, and poor patient prognosis in HCC patients. Gene set enrichment analysis suggested that patients with high LCLAT1 had significant enrichment for methylation‐, immune‐, and cell proliferation‐related pathways. The prognosis of HCC was found to be linked to the DNA methylation status of the five CpG islands within the LCLAT1 gene. Immune infiltration and single‐cell level analyses showed that LCLAT1 was closely associated with the tumor microenvironment. Moreover, high LCLAT1 expression may promote immune evasion in HCC, and the abundance of several immune cells correlated with HCC prognosis. Finally, HCC patients with low LCLAT1 responded better to treatment with transarterial chemoembolization, sorafenib, and immune checkpoint inhibitors. LCLAT1 might serve as a potential prognostic biomarker and as a multipathway target involved in the malignant progression of HCC. Importantly, LCLAT1 was related to immune infiltration and could aid in predicting treatment response in HCC.