Integrated bioinformatics analysis and experimental validation reveal the relationship between ALOX5AP and the prognosis and immune microenvironment in glioma.

in BMC medical genomics by Ping Song, Hui Deng, Yushu Liu, Mengxian Zhang

TLDR

  • ALOX5AP is a protein that helps convert arachidonic acid into leukotrienes, which are important for the immune system. The study found that ALOX5AP is highly expressed in gliomas and is associated with poor prognosis and immune microenvironment. The study also identified potential biomarkers for predicting prognosis and immunotherapy response in patients with glioma.

Abstract

Treatment of gliomas, the most prevalent primary malignant neoplasm of the central nervous system, is challenging. Arachidonate 5-lipoxygenase activating protein (ALOX5AP) is crucial for converting arachidonic acid into leukotrienes and is associated with poor prognosis in multiple cancers. Nevertheless, its relationship with the prognosis and the immune microenvironment of gliomas remains incompletely understood. The differential expression of ALOX5AP was evaluated based on public Databases. Kaplan-Meier, multivariate Cox proportional hazards regression analysis, time-dependent receiver operating characteristic, and nomogram were used to estimate the prognostic value of ALOX5AP. The relationship between ALOX5AP and immune infiltration was calculated using ESTIMATE and CIBERSORT algorithms. Relationships between ALOX5AP and human leukocyte antigen molecules, immune checkpoints, tumor mutation burden, TIDE score, and immunophenoscore were calculated to evaluate glioma immunotherapy response. Single gene GSEA and co-expression network-based GO and KEGG enrichment analysis were performed to explore the potential function of ALOX5AP. ALOX5AP expression was verified using multiplex immunofluorescence staining and its prognostic effects were confirmed using a glioma tissue microarray. ALOX5AP was highly expressed in gliomas, and the expression level was related to World Health Organization (WHO) grade, age, sex, IDH mutation status, 1p19q co-deletion status, MGMTp methylation status, and poor prognosis. Single-cell RNA sequencing showed that ALOX5AP was expressed in macrophages, monocytes, and T cells but not in tumor cells. ALOX5AP expression positively correlated with M2 macrophage infiltration and poor immunotherapy response. Immunofluorescence staining demonstrated that ALOX5AP was upregulated in WHO higher-grade gliomas, localizing to M2 macrophages. Glioma tissue microarray confirmed the adverse effect of ALOX5AP in the prognosis of glioma. ALOX5AP is highly expressed in M2 macrophages and may act as a potential biomarker for predicting prognosis and immunotherapy response in patients with glioma.

Overview

  • The study evaluates the differential expression of arachidonate 5-lipoxygenase activating protein (ALOX5AP) in gliomas and its relationship with the immune microenvironment and prognosis. The study uses public databases, including the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO), to analyze the expression of ALOX5AP in gliomas. The study also uses various statistical methods, such as Kaplan-Meier, multivariate Cox proportional hazards regression analysis, time-dependent receiver operating characteristic, and nomogram, to estimate the prognostic value of ALOXAP. The study also uses the ESTIMATE and CIBERSORT algorithms to calculate the relationship between ALOX5AP and immune infiltration. The study also evaluates the relationship between ALOX5AP and human leukocyte antigen molecules, immune checkpoints, tumor mutation burden, TIDE score, and immunophenoscore to evaluate glioma immunotherapy response. The study also performs single gene GSEA and co-expression network-based GO and KEGG enrichment analysis to explore the potential function of ALOX5AP. The study verifies the expression of ALOX5AP using multiplex immunofluorescence staining and confirms the adverse effect of ALOX5AP in the prognosis of glioma using a glioma tissue microarray.

Comparative Analysis & Findings

  • The study found that ALOX5AP expression was related to World Health Organization (WHO) grade, age, sex, IDH mutation status, 1p19q co-deletion status, MGMTp methylation status, and poor prognosis in gliomas. The study also found that ALOX5AP expression positively correlated with M2 macrophage infiltration and poor immunotherapy response. The study also found that ALOX5AP was highly expressed in M2 macrophages and may act as a potential biomarker for predicting prognosis and immunotherapy response in patients with glioma.

Implications and Future Directions

  • The study highlights the importance of ALOX5AP in the prognosis and immune microenvironment of gliomas. The study also identifies potential biomarkers for predicting prognosis and immunotherapy response in patients with glioma. The study suggests that further research is needed to validate the findings and to develop targeted therapies for gliomas.
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