Integration of single-cell and bulk RNA-seq to establish a predictive signature based on the differentiation trajectory of M2 macrophages in lung adenocarcinoma
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. How...
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.1010440/full |
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| author | Zhike Chen Zhike Chen Jian Yang Jian Yang Yu Li Yu Li Weibiao Zeng Weibiao Zeng Yiling Bai Cheng Ding Cheng Ding Chun Xu Chun Xu Chang Li Chang Li Jun Chen Jun Chen Sheng Ju Sheng Ju Lijuan Tang Lijuan Tang Jun Zhao Jun Zhao |
| author_facet | Zhike Chen Zhike Chen Jian Yang Jian Yang Yu Li Yu Li Weibiao Zeng Weibiao Zeng Yiling Bai Cheng Ding Cheng Ding Chun Xu Chun Xu Chang Li Chang Li Jun Chen Jun Chen Sheng Ju Sheng Ju Lijuan Tang Lijuan Tang Jun Zhao Jun Zhao |
| author_sort | Zhike Chen |
| collection | DOAJ |
| description | 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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| language | English |
| last_indexed | 2024-04-11T12:00:03Z |
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| series | Frontiers in Genetics |
| spelling | doaj.art-aab67356decf42458c1133e28ab3e0092022-12-22T04:24:53ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-09-011310.3389/fgene.2022.10104401010440Integration of single-cell and bulk RNA-seq to establish a predictive signature based on the differentiation trajectory of M2 macrophages in lung adenocarcinomaZhike Chen0Zhike Chen1Jian Yang2Jian Yang3Yu Li4Yu Li5Weibiao Zeng6Weibiao Zeng7Yiling Bai8Cheng Ding9Cheng Ding10Chun Xu11Chun Xu12Chang Li13Chang Li14Jun Chen15Jun Chen16Sheng Ju17Sheng Ju18Lijuan Tang19Lijuan Tang20Jun Zhao21Jun Zhao22Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, ChinaDalian Medical University, Dalian, Liaoning, ChinaDepartment of Pathology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, ChinaDepartment of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, ChinaBackground: 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.https://www.frontiersin.org/articles/10.3389/fgene.2022.1010440/fulllung adenocarcinomatumor microenvironment (TME)M2 macrophagesScRNA-seqimmunotherapy |
| spellingShingle | Zhike Chen Zhike Chen Jian Yang Jian Yang Yu Li Yu Li Weibiao Zeng Weibiao Zeng Yiling Bai Cheng Ding Cheng Ding Chun Xu Chun Xu Chang Li Chang Li Jun Chen Jun Chen Sheng Ju Sheng Ju Lijuan Tang Lijuan Tang Jun Zhao Jun Zhao Integration of single-cell and bulk RNA-seq to establish a predictive signature based on the differentiation trajectory of M2 macrophages in lung adenocarcinoma Frontiers in Genetics lung adenocarcinoma tumor microenvironment (TME) M2 macrophages ScRNA-seq immunotherapy |
| title | Integration of single-cell and bulk RNA-seq to establish a predictive signature based on the differentiation trajectory of M2 macrophages in lung adenocarcinoma |
| title_full | Integration of single-cell and bulk RNA-seq to establish a predictive signature based on the differentiation trajectory of M2 macrophages in lung adenocarcinoma |
| title_fullStr | Integration of single-cell and bulk RNA-seq to establish a predictive signature based on the differentiation trajectory of M2 macrophages in lung adenocarcinoma |
| title_full_unstemmed | Integration of single-cell and bulk RNA-seq to establish a predictive signature based on the differentiation trajectory of M2 macrophages in lung adenocarcinoma |
| title_short | Integration of single-cell and bulk RNA-seq to establish a predictive signature based on the differentiation trajectory of M2 macrophages in lung adenocarcinoma |
| title_sort | integration of single cell and bulk rna seq to establish a predictive signature based on the differentiation trajectory of m2 macrophages in lung adenocarcinoma |
| topic | lung adenocarcinoma tumor microenvironment (TME) M2 macrophages ScRNA-seq immunotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.1010440/full |
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