M2 macrophages secrete CXCL13 to promote renal cell carcinoma migration, invasion, and EMT

Xie, Yingwei; Chen, Zhiliang; Zhong, Qiyu; Zheng, Zijie; Chen, Yuqing; Shangguan, Wentai; Zhang, Yishan; Yang, Jingying; Zhu, Dingjun; Xie, Wenlian

doi:10.1186/s12935-021-02381-1

Cited by 35 publications

(16 citation statements)

References 48 publications

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“…M2 macrophages, CD8 + T cells, and fibroblasts were more abundant in the high-risk group than in the low-risk group. These immune cells were associated with the poor prognosis of patients with KIRC ( Davidsson et al, 2020 ; Komohara et al, 2011 ; Li et al, 2020 ; Nakayama et al, 2018 ; Xie et al, 2021 ; You et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…Exploring the molecular regulatory mechanisms of different subtypes has become a research hotspot in the field of cancer. m6A is the most common RNA methylation modification, and the molecular subtype based on m6A regulators can well-predict the efficacy of immunotherapy and evaluate the prognosis of patients (Shen et al, 2020;Zhong et al, 2021). 5mC, another type of methylation modification, can also wellpredict the prognosis of patients (Hu Y et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

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m7G regulator-mediated molecular subtypes and tumor microenvironment in kidney renal clear cell carcinoma

Chen

Nie²,

Gao³

et al. 2022

Front. Pharmacol.

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Background: RNA methylation modification plays an important role in immune regulation. m7G RNA methylation is an emerging research hotspot in the RNA methylation field. However, its role in the tumor immune microenvironment of kidney renal clear cell carcinoma (KIRC) is still unclear.Methods: We analyzed the expression profiles of 29 m7G regulators in KIRC, integrated multiple datasets to identify a novel m7G regulator-mediated molecular subtype, and developed the m7G score. We evaluated the immune tumor microenvironments in m7G clusters and analyzed the correlation of the m7G score with immune cells and drug sensitivity. We tested the predictive power of the m7G score for prognosis of patients with KIRC and verified the predictive accuracy of the m7G score by using the GSE40912 and E-MTAB-1980 datasets. The genes used to develop the m7G score were verified by qRT-PCR. Finally, we experimentally analyzed the effects of WDR4 knockdown on KIRC proliferation, migration, invasion, and drug sensitivity.Results: We identified three m7G clusters. The expression of m7G regulators was higher in cluster C than in other clusters. m7G cluster C was related to immune activation, low tumor purity, good prognosis, and low m7G score. Cluster B was related to drug metabolism, high tumor purity, poor survival, and high m7G score. Cluster A was related to purine metabolism. The m7G score can well-predict the prognosis of patients with KIRC, and its prediction accuracy based on the m7G score nomogram was very high. Patients with high m7G scores were more sensitive to rapamycin, gefitinib, sunitinib, and vinblastine than other patients. Knocking down WDR4 can inhibit the proliferation, migration, and invasion of 786-0 and Caki-1 cells and increase sensitivity to sorafenib and sunitinib.Conclusion: We proposed a novel molecular subtype related to m7G modification and revealed the immune cell infiltration characteristics of different subtypes. The developed m7G score can well-predict the prognosis of patients with KIRC, and our research provides a basis for personalized treatment of patients with KIRC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

m7G regulator-mediated molecular subtypes and tumor microenvironment in kidney renal clear cell carcinoma

Chen

Nie²,

Gao³

et al. 2022

Front. Pharmacol.

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“…M2 macrophages create an environment conducive to tumor survival by releasing growth factors, chemokines, and other inflammatory mediators ( Solinas et al, 2009 ; Lin et al, 2019 ). In addition, M2 macrophages can also promote tumor metastasis and invasion by promoting angiogenesis and other pathways ( Jetten et al, 2014 ; Xie et al, 2021 ). To further analyze the differences in composition and function within M2 macrophages, we used bioinformatics to perform an in-depth analysis at the single cell level.…”

Section: Discussionmentioning

confidence: 99%

Integration of single-cell and bulk RNA-seq to establish a predictive signature based on the differentiation trajectory of M2 macrophages in lung adenocarcinoma

et al. 2022

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Background: Tumor-associated macrophages as important members of the tumor microenvironment, are highly plastic and heterogeneous. TAMs can be classified into two preliminary subtypes: M1 and M2 macrophages. M2 macrophages are significantly associated with the progression of lung adenocarcinoma. However, no study has investigated the heterogeneity among M2 macrophages and their differentiation-related genes at the single-cell level to guide the clinical treatment of lung adenocarcinoma.Methods: Using the available annotation information from the Tumor Immune Single-cell Hub database, we clustered and annotated 12 lung adenocarcinoma samples using the R package ‘Seurat’. Subsequently, we extracted M2 macrophages for secondary clustering analysis and performed cell trajectory analysis using the R package ‘monocle2’. Based on heterogeneous genes associated with the differentiation trajectory of M2 macrophages, we established a prognostic lung adenocarcinoma model using Lasso-Cox and multivariate stepwise regression. In addition, we also performed immunotherapy and chemotherapy predictions.Results: M2 macrophages exhibit heterogeneity among themselves. M2 macrophages in different differentiation states showed significant differences in pathway activation and immune cell communication. Prognostic signature based on heterogeneous genes can be used to classify the prognostic status and abundance of immune cell infiltration in lung adenocarcinoma patients. In addition, the calculation of the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm and the validation of the GSE126044 database indicated that lung adenocarcinoma patients with high-risk scores had poorer treatment outcomes when receiving immune checkpoint inhibitors treatment.Conclusion: Based on scRNA-seq and Bulk-seq data, we identified M2 macrophage-associated prognostic signature with a potential clinical utility to improve precision therapy.

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“…Numerous studies have suggested that CCL2 and CCL5 could promote M2 macrophages generation in TME ( Smida et al, 2020 ; Kang et al, 2021 ). M2 macrophages secreted chemokines such as CCL17 and CXCL13 ( Liu Y. et al, 2020 ; Xie et al, 2021 ). Meanwhile, CCL19 and CCL21 were shown to be associated with M1 macrophage chemotaxis ( Xuan et al, 2015 ; Boibessot et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Glycolysis-Related LINC02432/Hsa-miR-98–5p/HK2 Axis Inhibits Ferroptosis and Predicts Immune Infiltration, Tumor Mutation Burden, and Drug Sensitivity in Pancreatic Adenocarcinoma

Tan

Liu

et al. 2022

Front. Pharmacol.

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Pancreatic adenocarcinoma (PAAD) is a malignant cancer with high incidence and mortality. Glycometabolic rearrangements (aerobic glycolysis) is a hallmark of PAAD and contributes to tumorigenesis and progression through numerous mechanisms. This study aimed to identify a novel glycolysis-related lncRNA-miRNA-mRNA ceRNA signature in PAAD and explore its potential molecular function. We first calculated the glycolysis score for each PAAD patient by the ssGSEA algorithm and found that patients with higher hallmark glycolysis scores had poorer prognosis. Subsequently, we obtained a novel glycolysis-related LINC02432/hsa-miR-98–5p/HK2 axis from the TCGA and GEO databases using comprehensive bioinformatics analysis and developed a nomogram to predict overall survival. Furthermore, functional characterization analysis revealed that LINC02432/hsa-miR-98–5p/HK2 axis risk score was negatively correlated with ferroptosis. The tumor immune infiltration analysis suggested positive correlations between ceRNA risk score and infiltrated M0 macrophage levels in PAAD. Correlation analysis found that ceRNA risk scores were positively correlated with four chemokines (CXCL3, CXCL5, CXCL8 and CCL20) and one immune checkpoint gene (SIGLEC15). Meanwhile, tumor mutation burden (TMB), an indicator for predicting response to immunotherapy, was positively correlated with ceRNA risk score. Finally, the drug sensitivity analysis showed that the high-risk score patients might be more sensitive to EGFR, MEK and ERK inhibitors than low-risk score patients. In conclusion, our study suggested that LINC02432/hsa-miR-98–5p/HK2 axis may serve as a novel diagnostic, prognostic, and therapeutic target in PAAD treatment.

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M2 macrophages secrete CXCL13 to promote renal cell carcinoma migration, invasion, and EMT

Cited by 35 publications

References 48 publications

m7G regulator-mediated molecular subtypes and tumor microenvironment in kidney renal clear cell carcinoma

m7G regulator-mediated molecular subtypes and tumor microenvironment in kidney renal clear cell carcinoma

Integration of single-cell and bulk RNA-seq to establish a predictive signature based on the differentiation trajectory of M2 macrophages in lung adenocarcinoma

Glycolysis-Related LINC02432/Hsa-miR-98–5p/HK2 Axis Inhibits Ferroptosis and Predicts Immune Infiltration, Tumor Mutation Burden, and Drug Sensitivity in Pancreatic Adenocarcinoma

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