Discovering the Potential Role of the C2 DUSP2+ MCs Subgroup in Lung Adenocarcinoma
Objective: In both industrialized and developing nations worldwide, lung adenocarcinoma is one of the deadliest malignant tumors and the primary cause of cancer-related deaths. Its cellular heterogeneity is unclear to the fullest extent, although in recent years, its prevalence in younger individual...
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| Language: | English |
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Elsevier
2025-04-01
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| Series: | Translational Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523325000269 |
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| author | Shengyi Zhang Xinhan Li Zhikai Xiahou Ailing Chen Renfang Sun Chao Liu Jie Yuan |
| author_facet | Shengyi Zhang Xinhan Li Zhikai Xiahou Ailing Chen Renfang Sun Chao Liu Jie Yuan |
| author_sort | Shengyi Zhang |
| collection | DOAJ |
| description | Objective: In both industrialized and developing nations worldwide, lung adenocarcinoma is one of the deadliest malignant tumors and the primary cause of cancer-related deaths. Its cellular heterogeneity is unclear to the fullest extent, although in recent years, its prevalence in younger individuals has increased. Therefore, it is urgent to deepen the understanding of lung adenocarcinoma and explore new therapeutic methods. Methods: CytoTRACE, Monocle, SCENIC, and enrichment analysis were used to analyze the single cell RNA data, we characterized the biological characteristics of mast cells (MCs) in lung adenocarcinoma patient samples. CellChat was used to analyze and validate the interaction between MCs and tumor cells in lung adenocarcinoma. Prognostic models were used to evaluate and predict the development trend and outcome of a patient's disease, such as the survival time of cancer patients. The python package SCENIC was used to evaluate the enrichment of transcription factors and the activity of regulators in lung adenocarcinoma cell subgroups. CCK-8 assay could validate the activity of a specific cell subgroup sequenced in single cell sequencing to confirm the role of this cell subgroup in tumor proliferation. Results: Our analysis identified seven major cell types, further grouping MCs within them and identifying four distinct subgroups, including MCs with high DUSP2 expression, which showed some tumor-related characteristics. In addition, we identified the key signaling receptor EGFR and validated it through in vitro knockdown experiments, demonstrating its role in promoting cancer. In addition, we established an independent prognostic indicator, the DUSP2+ MCs risk score, which showed an association between groups with high risk scores and poor outcomes. Conclusion: These findings shed light on the complex interactions in the lung adenocarcinoma tumor microenvironment and suggest that targeting specific MCs subgroups, particularly through the EGFR signaling pathway, may provide new therapeutic strategies. |
| format | Article |
| id | doaj-art-f03f91aadb6046f8a415ab4e05ddabb9 |
| institution | OA Journals |
| issn | 1936-5233 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj-art-f03f91aadb6046f8a415ab4e05ddabb92025-08-20T02:11:05ZengElsevierTranslational Oncology1936-52332025-04-015410229510.1016/j.tranon.2025.102295Discovering the Potential Role of the C2 DUSP2+ MCs Subgroup in Lung AdenocarcinomaShengyi Zhang0Xinhan Li1Zhikai Xiahou2Ailing Chen3Renfang Sun4Chao Liu5Jie Yuan6Department of Thoracic Surgery, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 201600, ChinaThe First Clinical Medical College of Shandong University of Traditional Chinese Medicine, Jinan, ChinaChina Institute of Sport and Health Science, Beijing Sport University, Beijing, ChinaQuality Control Department, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 201600, China; Corresponding authors.Department of Thoracic Surgery, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 201600, China; Corresponding authors.Department of Orthopaedics, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Corresponding authors.Sijing Town Community Healthcare Center, Shanghai, China; Corresponding authors.Objective: In both industrialized and developing nations worldwide, lung adenocarcinoma is one of the deadliest malignant tumors and the primary cause of cancer-related deaths. Its cellular heterogeneity is unclear to the fullest extent, although in recent years, its prevalence in younger individuals has increased. Therefore, it is urgent to deepen the understanding of lung adenocarcinoma and explore new therapeutic methods. Methods: CytoTRACE, Monocle, SCENIC, and enrichment analysis were used to analyze the single cell RNA data, we characterized the biological characteristics of mast cells (MCs) in lung adenocarcinoma patient samples. CellChat was used to analyze and validate the interaction between MCs and tumor cells in lung adenocarcinoma. Prognostic models were used to evaluate and predict the development trend and outcome of a patient's disease, such as the survival time of cancer patients. The python package SCENIC was used to evaluate the enrichment of transcription factors and the activity of regulators in lung adenocarcinoma cell subgroups. CCK-8 assay could validate the activity of a specific cell subgroup sequenced in single cell sequencing to confirm the role of this cell subgroup in tumor proliferation. Results: Our analysis identified seven major cell types, further grouping MCs within them and identifying four distinct subgroups, including MCs with high DUSP2 expression, which showed some tumor-related characteristics. In addition, we identified the key signaling receptor EGFR and validated it through in vitro knockdown experiments, demonstrating its role in promoting cancer. In addition, we established an independent prognostic indicator, the DUSP2+ MCs risk score, which showed an association between groups with high risk scores and poor outcomes. Conclusion: These findings shed light on the complex interactions in the lung adenocarcinoma tumor microenvironment and suggest that targeting specific MCs subgroups, particularly through the EGFR signaling pathway, may provide new therapeutic strategies.http://www.sciencedirect.com/science/article/pii/S1936523325000269Single cell RNA sequencingLung adenocarcinomaRisk scoreTumor microenvironmentDiagnosis |
| spellingShingle | Shengyi Zhang Xinhan Li Zhikai Xiahou Ailing Chen Renfang Sun Chao Liu Jie Yuan Discovering the Potential Role of the C2 DUSP2+ MCs Subgroup in Lung Adenocarcinoma Translational Oncology Single cell RNA sequencing Lung adenocarcinoma Risk score Tumor microenvironment Diagnosis |
| title | Discovering the Potential Role of the C2 DUSP2+ MCs Subgroup in Lung Adenocarcinoma |
| title_full | Discovering the Potential Role of the C2 DUSP2+ MCs Subgroup in Lung Adenocarcinoma |
| title_fullStr | Discovering the Potential Role of the C2 DUSP2+ MCs Subgroup in Lung Adenocarcinoma |
| title_full_unstemmed | Discovering the Potential Role of the C2 DUSP2+ MCs Subgroup in Lung Adenocarcinoma |
| title_short | Discovering the Potential Role of the C2 DUSP2+ MCs Subgroup in Lung Adenocarcinoma |
| title_sort | discovering the potential role of the c2 dusp2 mcs subgroup in lung adenocarcinoma |
| topic | Single cell RNA sequencing Lung adenocarcinoma Risk score Tumor microenvironment Diagnosis |
| url | http://www.sciencedirect.com/science/article/pii/S1936523325000269 |
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