Pan-cancer analysis identifies LPCATs family as a prognostic biomarker and validation of LPCAT4/WNT/β-catenin/c-JUN/ACSL3 in hepatocellular carcinoma

Abstract

Lipid remodeling regulators are now being investigated as potential therapeutic targets for cancer therapy as a result of their involvement, which includes promoting cancer cells’ adaptation to the restricted environment. Lysophosphatidylcholine acyltransferases (LPCATs, LPCAT1-4) are enzymes that regulate the remodeling of bio-membranes. The functions of these enzymes in cancer are largely unknown. In the current study, we found that genes belonging to the LPCAT family participated in tumor advancement and were strongly linked to dismal prognosis in many different malignancies. We constructed the LPCATs scores model and explored this model in pan-cancer. Malignant pathways in pan-cancer were positively related to LPCATs scores, and all pathways had strong links to the tumor microenvironment (TME). Multiple immune-associated features of the TME in pan-cancer were likewise associated with higher LPCATs scores. In addition, the LPCATs score functioned as a prognostic marker for immune checkpoint inhibitor (ICI) therapies in patients with cancer. LPCAT4 enhanced cell growth and cholesterol biosynthesis by up-regulating ACSL3 in hepatocellular carcinoma (HCC). WNT/β-catenin/c-JUN signaling pathway mediated LPCAT4’s regulation on ACSL3. These findings demonstrated that genes in the LPCAT family might be used as cancer immunotherapy and prognosis-related biomarkers. Specifically, LPCAT4 could be a treatment target of HCC.

Phospholipid Acyltransferases: Characterization and Involvement of the Enzymes in Metabolic and Cancer Diseases

“…Its increased expression in hepatocellular carcinoma is associated with a worse prognosis, suggesting a potential role as a therapeutic target for this cancer [ 18 , 133 ]. LPCAT4 is also implicated in cancer, with its expression decreased in colorectal cancer, suggesting an anticancer nature [ 74 ].…”