Prognostic value of LPAR1 expression and methylation in low-grade gliomas: a meta-analysis of TCGA and CGGA datasets and functional validation

TL;DR

This study shows that low LPAR1 expression or high methylation is linked to better survival in low-grade gliomas and affects tumor immunity and cell behavior.

Contribution

The study identifies LPAR1 methylation and expression as novel prognostic markers and explores their functional role in glioma progression and immune regulation.

Findings

High LPAR1 methylation is associated with better overall and progression-free survival in low-grade gliomas.

Low LPAR1 expression correlates with age, histological type, and IDH mutation status in glioma patients.

LPAR1 overexpression promotes tumor cell proliferation and migration, while its knockdown has the opposite effect.

Abstract

Lysophosphatidic acid receptor 1 (LPAR1) mediates various biological behaviors in physiological and pathological processes. This study aims to comprehensively evaluate the prognostic value of LPAR1 expression and methylation in LGG, and explore their functional effects on tumor progression and immune regulation.

The GEO database was used to analyze LPAR1 expression in tumors and normal tissues. The TCGA-LGG and CGGA datasets were used to analyze the expression, methylation, immunity and prognostic significance of LGG. Immune cells and immune pathways were detected by flow cytometry, ELISA and western blot analysis. The role of LPAR1 in LGG was validated by RT-PCR, TUNEL assay, CCK-8 assay, flow cytometry, wound healing assay and transwell assay.

We included 627 patients who contained complete information required for analysis in the TCGA-LGG and CGGA datasets. Methylation of the LPAR1 promoter suppresses its expression. High methylation levels were associated with better overall survival (OS) and progression-free survival (PFS) (P < 0.05) in LGG. Decreased LPAR1 expression and increased methylation levels were significantly associated with age, histological types and isocitrate dehydrogenase (IDH) mutation status (P < 0.05). Multivariate analysis showed that LPAR1 was an independent prognostic factor for LGG (P = 0.002). Meta-analysis showed that high LPAR1 expression was indeed a poor prognosis for patients’ OS in LGG (HR, 1.06; 95% CI, 0.95–1.17). Low LPAR1 expression affected the proportion of tumor immune infiltrating cells (TIICs) in the tumor microenvironment (TME), which was related to the involvement of LPAR1 in pathways such as CSK and Th1/Th2. In the cell experiment, LPAR1 overexpression promoted proliferation, migration, and invasion and inhibited apoptosis, whereas LPAR1 knockdown exhibited the opposite effect.

Low LPAR1 expression or high LPAR1 methylation level was a potential prognostic molecular marker for favorable survival in LGG. Moreover, we identified a regulatory pattern in which a high level of LPAR1 methylation resulted in a decrease in LPAR1 expression, which affected the proportion of TIICs in TME. This pattern may work through CSK and Th1/Th2 pathways. Inhibiting LPAR1 can suppress the biological behavior of glioma cells in vitro. These findings open up new avenues for therapeutic and prognostic evaluation of LGG.

The online version contains supplementary material available at 10.1186/s12885-025-15406-z.

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