Single-Cell RNA Sequencing Analysis of Gene Regulatory Network Changes in the Development of Lung Adenocarcinoma
Lung cancer is a highly heterogeneous disease. Cancer cells and other cells within the tumor microenvironment interact to determine disease progression, as well as response to or escape from treatment. Understanding the regulatory relationship between cancer cells and their tumor microenvironment in...
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MDPI AG
2023-04-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/13/4/671 |
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| author | Dongshuo Yu Siwen Zhang Zhenhao Liu Linfeng Xu Lanming Chen Lu Xie |
| author_facet | Dongshuo Yu Siwen Zhang Zhenhao Liu Linfeng Xu Lanming Chen Lu Xie |
| author_sort | Dongshuo Yu |
| collection | DOAJ |
| description | Lung cancer is a highly heterogeneous disease. Cancer cells and other cells within the tumor microenvironment interact to determine disease progression, as well as response to or escape from treatment. Understanding the regulatory relationship between cancer cells and their tumor microenvironment in lung adenocarcinoma is of great significance for exploring the heterogeneity of the tumor microenvironment and its role in the genesis and development of lung adenocarcinoma. This work uses public single-cell transcriptome data (distant normal, nLung; early LUAD, tLung; advanced LUAD, tL/B), to draft a cell map of lung adenocarcinoma from onset to progression, and provide a cell-cell communication view of lung adenocarcinoma in the different disease stages. Based on the analysis of cell populations, it was found that the proportion of macrophages was significantly reduced in the development of lung adenocarcinoma, and patients with lower proportions of macrophages exhibited poor prognosis. We therefore constructed a process to screen an intercellular gene regulatory network that reduces any error generated by single cell communication analysis and increases the credibility of selected cell communication signals. Based on the key regulatory signals in the macrophage-tumor cell regulatory network, we performed a pseudotime analysis of the macrophages and found that signal molecules (TIMP1, VEGFA, SPP1) are highly expressed in immunosuppression-associated macrophages. These molecules were also validated using an independent dataset and were significantly associated with poor prognosis. Our study provides an effective method for screening the key regulatory signals in the tumor microenvironment and the selected signal molecules may serve as a reference to guide the development of diagnostic biomarkers for risk stratification and therapeutic targets for lung adenocarcinoma. |
| first_indexed | 2024-03-11T05:12:30Z |
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| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-11T05:12:30Z |
| publishDate | 2023-04-01 |
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| series | Biomolecules |
| spelling | doaj.art-e1c825c21bdb4ab2a66ca6f71fdb32a32023-11-17T18:29:42ZengMDPI AGBiomolecules2218-273X2023-04-0113467110.3390/biom13040671Single-Cell RNA Sequencing Analysis of Gene Regulatory Network Changes in the Development of Lung AdenocarcinomaDongshuo Yu0Siwen Zhang1Zhenhao Liu2Linfeng Xu3Lanming Chen4Lu Xie5Key Laboratory of Quality and Safety Risk Assessment for Aquatic Products on Storage and Preservation (Shanghai), China Ministry of Agriculture, College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, ChinaShanghai-MOST Key Laboratory of Health and Disease Genomics (Chinese National Human Genome Center at Shanghai), Institute of Genome and Bioinformatics, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai 200037, ChinaShanghai-MOST Key Laboratory of Health and Disease Genomics (Chinese National Human Genome Center at Shanghai), Institute of Genome and Bioinformatics, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai 200037, ChinaShanghai-MOST Key Laboratory of Health and Disease Genomics (Chinese National Human Genome Center at Shanghai), Institute of Genome and Bioinformatics, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai 200037, ChinaKey Laboratory of Quality and Safety Risk Assessment for Aquatic Products on Storage and Preservation (Shanghai), China Ministry of Agriculture, College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, ChinaShanghai-MOST Key Laboratory of Health and Disease Genomics (Chinese National Human Genome Center at Shanghai), Institute of Genome and Bioinformatics, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai 200037, ChinaLung cancer is a highly heterogeneous disease. Cancer cells and other cells within the tumor microenvironment interact to determine disease progression, as well as response to or escape from treatment. Understanding the regulatory relationship between cancer cells and their tumor microenvironment in lung adenocarcinoma is of great significance for exploring the heterogeneity of the tumor microenvironment and its role in the genesis and development of lung adenocarcinoma. This work uses public single-cell transcriptome data (distant normal, nLung; early LUAD, tLung; advanced LUAD, tL/B), to draft a cell map of lung adenocarcinoma from onset to progression, and provide a cell-cell communication view of lung adenocarcinoma in the different disease stages. Based on the analysis of cell populations, it was found that the proportion of macrophages was significantly reduced in the development of lung adenocarcinoma, and patients with lower proportions of macrophages exhibited poor prognosis. We therefore constructed a process to screen an intercellular gene regulatory network that reduces any error generated by single cell communication analysis and increases the credibility of selected cell communication signals. Based on the key regulatory signals in the macrophage-tumor cell regulatory network, we performed a pseudotime analysis of the macrophages and found that signal molecules (TIMP1, VEGFA, SPP1) are highly expressed in immunosuppression-associated macrophages. These molecules were also validated using an independent dataset and were significantly associated with poor prognosis. Our study provides an effective method for screening the key regulatory signals in the tumor microenvironment and the selected signal molecules may serve as a reference to guide the development of diagnostic biomarkers for risk stratification and therapeutic targets for lung adenocarcinoma.https://www.mdpi.com/2218-273X/13/4/671gene regulatory networklung adenocarcinomasingle-cell transcriptome analysismacrophagecell-cell communication |
| spellingShingle | Dongshuo Yu Siwen Zhang Zhenhao Liu Linfeng Xu Lanming Chen Lu Xie Single-Cell RNA Sequencing Analysis of Gene Regulatory Network Changes in the Development of Lung Adenocarcinoma Biomolecules gene regulatory network lung adenocarcinoma single-cell transcriptome analysis macrophage cell-cell communication |
| title | Single-Cell RNA Sequencing Analysis of Gene Regulatory Network Changes in the Development of Lung Adenocarcinoma |
| title_full | Single-Cell RNA Sequencing Analysis of Gene Regulatory Network Changes in the Development of Lung Adenocarcinoma |
| title_fullStr | Single-Cell RNA Sequencing Analysis of Gene Regulatory Network Changes in the Development of Lung Adenocarcinoma |
| title_full_unstemmed | Single-Cell RNA Sequencing Analysis of Gene Regulatory Network Changes in the Development of Lung Adenocarcinoma |
| title_short | Single-Cell RNA Sequencing Analysis of Gene Regulatory Network Changes in the Development of Lung Adenocarcinoma |
| title_sort | single cell rna sequencing analysis of gene regulatory network changes in the development of lung adenocarcinoma |
| topic | gene regulatory network lung adenocarcinoma single-cell transcriptome analysis macrophage cell-cell communication |
| url | https://www.mdpi.com/2218-273X/13/4/671 |
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