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Proteomic Analysis of Human Macrophage Polarization Under a Low Oxygen Environment
Published on: January 7, 2019
ALKBH5 modulates macrophages polarization in tumor microenvironment of ovarian cancer
1Gynecological Mini-Invasive Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, 17 Qihelou Street, Beijing, 100006, China.
Background:
Macrophages play an essential role in regulating ovarian cancer immune microenvironment. Studies have shown that m6A methylation could influence immune microenvironment in cancer. In this study, we investigated the roles of m6A demethylase ALKBH5 and m6A recognition protein IGF2BP2 played in regulating macrophages polarization in ovarian cancer.
Methods:
In this study, we first explored the differentially expressed m6A methylation enzymes in M0 and M2 macrophages according to two independent GEO datasets. TIMER2.0 and GSCA database were used to explore the immune analysis of ALKBH5 and IGF2BP2 in ovarian cancer. K-M plotter and TIMER2.0 databases were used to evaluate the prognostic role of ALKBH5 and IGF2BP2 in ovarian cancer. For CNV mutation analysis of ALKBH5 and IGF2BP2, cBioPortal and GSCA databases were used. For single-cell analysis, sc-TIME and HPA softwares were used to analyze the roles of ALKBH5 and IGF2BP2 played in immune cells in ovarian cancer. To identify the role of ALKBH5 played in macrophage polarization, RT-PCR was used to verify the macrophage polarization related markers in vitro study. The function of ALKBH5 played in ovarian cancer was further analyzed through GO and KEGG analysis.
Findings:
In this study, we found that ALKBH5 and IGF2BP2 were up-regulated in M2 macrophages, which showed closely correlation with immune cells expressions in ovarian cancer, especially with macrophages. Ovarian cancer patients with higher expression of ALKBH5 and IGF2BP2 showed worse prognosis, possibly because of their close correlation with immune response. ALKBH5 also correlated with macrophage phenotypes in single-cell levels analysis. However, the expression level of IGF2BP2 in ovarian cancer immune microenvironment was very low. The results of RT-PCR indicated the potential role of ALKBH5 in M2 polarization of macrophages.
Interpretation:
ALKBH5 participated in regulating macrophage M2 polarization in ovarian cancer immune microenvironment.
Insights
The m6A demethylase ALKBH5 regulates M2 macrophage polarization in ovarian cancer, impacting the immune microenvironment and patient prognosis. IGF2BP2 showed low expression and was less significant in this context.
Area of Science:
- Oncology
- Immunology
- Epigenetics
Background:
- Macrophages are key regulators of the ovarian cancer immune microenvironment.
- N6-methyladenosine (m6A) methylation influences cancer immunity.
- Investigating m6A regulators ALKBH5 and IGF2BP2 in ovarian cancer macrophage polarization is crucial.
Purpose of the Study:
- To explore the roles of m6A demethylase ALKBH5 and m6A recognition protein IGF2BP2 in regulating macrophage polarization within the ovarian cancer immune microenvironment.
- To assess the correlation of ALKBH5 and IGF2BP2 expression with immune cell infiltration and patient prognosis in ovarian cancer.
Main Methods:
- Differential expression analysis of m6A enzymes in M0 vs. M2 macrophages using GEO datasets.
- Immune and prognostic analyses utilizing TIMER2.0, GSCA, and K-M plotter databases.
- CNV mutation analysis via cBioPortal and GSCA; single-cell analysis with sc-TIME and HPA.
- In vitro RT-PCR to verify macrophage polarization markers and GO/KEGG analysis for ALKBH5 function.
Main Results:
- ALKBH5 and IGF2BP2 were upregulated in M2 macrophages and correlated with immune cell expression, particularly macrophages, in ovarian cancer.
- Higher ALKBH5 and IGF2BP2 expression correlated with worse prognosis in ovarian cancer patients, linked to immune response.
- ALKBH5 showed correlation with macrophage phenotypes at the single-cell level; RT-PCR suggested ALKBH5's role in M2 polarization. IGF2BP2 expression was minimal in the ovarian cancer immune microenvironment.
Conclusions:
- ALKBH5 plays a significant role in regulating M2 macrophage polarization within the ovarian cancer immune microenvironment.
- The findings highlight ALKBH5 as a potential therapeutic target for modulating the ovarian cancer immune response.
