LPCAT3 is a potential prognostic biomarker and may be correlated with immune infiltration and ferroptosis in acute myeloid leukemia: a pan-cancer analysis

Abstract

Background: Recent studies have highlighted the critical role of lysophosphatidylcholine acyltransferase 3 (LPCAT3) during cancer development. However, the abnormal expression and prognostic significance of pan-cancer have not been determined. Methods: We explored the expression level and prognostic value of LPCAT3 in 33 cancers by bioinformatics techniques, and comprehensively studied the biological function and immune infiltration based on the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases as well as many online websites. Results: LPCAT3 is significantly upregulated in many cancers, and it is associated with prognosis. Pan-cancer Cox regression analysis indicated that the high expression of LPCAT3 was associated with poor prognosis in acute myeloid leukemia (AML), lower-grade glioma (LGG), ovarian cancer (OV), and uveal melanoma (UVM), while better prognosis in kidney renal clear cell carcinoma (KIRC) (all P<0.05). Further analysis indicated that higher LPCAT3 expression in most cancers markedly decreased the infiltration of immune cells, except diffuse large B-cell lymphoma (DLBC), AML, LGG, stomach adenocarcinoma (STAD), and UVM. In contrast, the expression level of LPCAT3 was positively correlated with most immune checkpoints in colon adenocarcinoma (COAD), DLBC, LGG, liver hepatocellular carcinoma (LIHC), and UVM. Additionally, LPCAT3 expression was associated with tumor mutational burden (TMB) in 4 cancer types, while microsatellite instability (MSI) was in 3 cancer types. Functional enrichment analysis showed LPCAT3 upregulation was highly associated with lipid metabolism and ferroptosis processes. In addition, the result of prediction drug response suggested that B-cell lymphoma 2 (BCL2) inhibitors and Midostaurin may be a potential treatment option for AML with low-LPCAT3 expression. Conclusions: LPCAT3 expression is increased in multiple cancers. Overexpression of LPCAT3 is associated with poor prognosis and tumor immune microenvironment in many cancers, especially in AML. Our results showed that the oncogene of LPCAT3 may serve as a potential prognostic biomarker and/or therapeutic target in AML patients.