Monoacylglycerol lipase regulates macrophage polarization and cancer progression in uveal melanoma and pan-cancer

Yao Tan; Juan Pan; Zhenjun Deng; Tao Chen; Jinquan Xia; Ziling Liu; Chang Zou; Bo Qin

doi:10.3389/fimmu.2023.1161960

Monoacylglycerol lipase regulates macrophage polarization and cancer progression in uveal melanoma and pan-cancer

Front Immunol. 2023 Mar 23:14:1161960. doi: 10.3389/fimmu.2023.1161960. eCollection 2023.

Authors

Yao Tan¹, Juan Pan^{2

3}, Zhenjun Deng^{4

5}, Tao Chen⁶, Jinquan Xia³, Ziling Liu^{1

7}, Chang Zou⁸, Bo Qin^{1

9}

Affiliations

¹ Shenzhen Aier Eye Hospital, Aier Eye Hospital, Jinan University, Shenzhen, China.
² National Center for International Research of Bio-targeting Theranostics, Guangxi Key Laboratory of Bio-targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Talent Highland of Bio-targeting Theranostics, Guangxi Medical University, Nanning, Guangxi, China.
³ Department of Clinical Medical Research Center, The Second Clinical Medical College, The First Affiliated Hospital of Southern University of Science and Technology, Jinan University (Shenzhen People's Hospital), Shenzhen, Guangdong, China.
⁴ Department of Dermatology, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, China.
⁵ The First Affiliated Hospital, Jinan University, Guangzhou, China.
⁶ School of Medicine, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, China.
⁷ Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, China.
⁸ School of Life and Health Sciences, The Chinese University of Kong Hong, Shenzhen, China.
⁹ Shenzhen Aier Ophthalmic Technology Institute, Shenzhen, China.

Abstract

Background: Although lipid metabolism has been proven to play a key role in the development of cancer, its significance in uveal melanoma (UM) has not yet been elucidated in the available literature.

Methods: To identify the expression patterns of lipid metabolism in 80 UM patients from the TCGA database, 47 genes involved in lipid metabolism were analyzed. Consensus clustering revealed two distinct molecular groups. ESTIMATE, TIMER, and ssGSEA analyses were done to identify the differences between the two subgroups in tumor microenvironment (TME) and immune state. Using Cox regression and Lasso regression analysis, a risk model based on differentially expressed genes (DEGs) was developed. To validate the expression of monoacylglycerol lipase (MGLL) and immune infiltration in diverse malignancies, a pan-cancer cohort from the UCSC database was utilized. Next, a single-cell sequencing analysis on UM patients from the GEO data was used to characterize the lipid metabolism in TME and the role of MGLL in UM. Finally, in vitro investigations were utilized to study the involvement of MGLL in UM.

Results: Two molecular subgroups of UM patients have considerably varied survival rates. The majority of DEGs between the two subgroups were associated with immune-related pathways. Low immune scores, high tumor purity, a low number of immune infiltrating cells, and a comparatively low immunological state were associated with a more favorable prognosis. An examination of GO and KEGG data demonstrated that the risk model based on genes involved with lipid metabolism can accurately predict survival in patients with UM. It has been demonstrated that MGLL, a crucial gene in this paradigm, promotes the proliferation, invasion, and migration of UM cells. In addition, we discovered that MGLL is strongly expressed in macrophages, specifically M2 macrophages, which may play a function in the M2 polarization of macrophages and M2 macrophage activation in cancer cells.

Conclusion: This study demonstrates that the risk model based on lipid metabolism may be useful for predicting the prognosis of patients with UM. By promoting macrophage M2 polarization, MGLL contributes to the evolution of malignancy in UM, suggesting that it may be a therapeutic target for UM.

Keywords: cancer prognosis; lipid metabolism; macrophage polarization; monoacylglycerol lipase (MGLL); tumor microenvironment (TME); uveal melanoma (UM).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Humans
Macrophage Activation
Macrophages
Melanoma* / genetics
Monoacylglycerol Lipases* / genetics
Tumor Microenvironment

Substances

Monoacylglycerol Lipases

Supplementary concepts

Uveal melanoma

Grants and funding

This work was supported by the Science Research Foundation of Shenzhen Aier Eye Hospital (SZAE2020B04), the Science Research Grant of Aier Eye Hospital Group (AM2001D2, AF2001D9, AM2101D1), the Natural Science Foundation of Guangdong Province, China (2022A1515010742), and Hunan Provincial Natural Science Foundation of China (2021JJ30045).