Selective inhibition of TGF-β-induced epithelial-mesenchymal transition overcomes chemotherapy resistance in high-risk lung squamous cell carcinoma
Abstract Lung squamous cell carcinoma (LUSC) represents a major subtype of lung cancer, and it demonstrates limited treatment options and worse survival. Identifications of a prognostic model and chemoresistance mechanism can be helpful for improving stratification and guiding therapy decisions. The...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-02-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07595-x |
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| author | Liangdong Sun Jue Wang Huansha Yu Xinsheng Zhu Jing Zhang Junjie Hu Yilv Yan Xun Zhang Yuming Zhu Gening Jiang Ming Ding Peng Zhang Lele Zhang |
| author_facet | Liangdong Sun Jue Wang Huansha Yu Xinsheng Zhu Jing Zhang Junjie Hu Yilv Yan Xun Zhang Yuming Zhu Gening Jiang Ming Ding Peng Zhang Lele Zhang |
| author_sort | Liangdong Sun |
| collection | DOAJ |
| description | Abstract Lung squamous cell carcinoma (LUSC) represents a major subtype of lung cancer, and it demonstrates limited treatment options and worse survival. Identifications of a prognostic model and chemoresistance mechanism can be helpful for improving stratification and guiding therapy decisions. The integrative development of machine learning-based models reveals a random survival forest (RSF) prognostic model for LUSC. The 12-gene RSF model exhibits high prognostic power in more than 1,000 LUSC patients. High-risk LUSC patients are associated with worse survival and the activation of the epithelial-mesenchymal transition pathway. Additionally, high-risk LUSC patients are resistant to docetaxel or vinorelbine treatment. In vitro and in vivo drug sensitivity experiments indicates that high-risk HCC15/H226 tumour cells and cell line-derived xenograft models are more resistant to vinorelbine treatment. Furthermore, the combination of chemotherapy with transforming growth factor-β inhibition augments antitumour responses in LUSC tumours. Our study provides valuable insights into prognosis stratification and the development of therapeutic strategies for LUSC. |
| format | Article |
| id | doaj-art-0d44756497d449bb9ff0fbb3380012ff |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-0d44756497d449bb9ff0fbb3380012ff2025-02-02T12:37:28ZengNature PortfolioCommunications Biology2399-36422025-02-018111210.1038/s42003-025-07595-xSelective inhibition of TGF-β-induced epithelial-mesenchymal transition overcomes chemotherapy resistance in high-risk lung squamous cell carcinomaLiangdong Sun0Jue Wang1Huansha Yu2Xinsheng Zhu3Jing Zhang4Junjie Hu5Yilv Yan6Xun Zhang7Yuming Zhu8Gening Jiang9Ming Ding10Peng Zhang11Lele Zhang12Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji UniversityDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji UniversityDepartment of Animal Experimental Center, Shanghai Pulmonary Hospital, School of Medicine, Tongji UniversityDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji UniversityDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji UniversityDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji UniversityDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji UniversityDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji UniversityDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji UniversityDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji UniversitySchool of Life Science and Technology, China Pharmaceutical UniversityDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji UniversityCentral Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji UniversityAbstract Lung squamous cell carcinoma (LUSC) represents a major subtype of lung cancer, and it demonstrates limited treatment options and worse survival. Identifications of a prognostic model and chemoresistance mechanism can be helpful for improving stratification and guiding therapy decisions. The integrative development of machine learning-based models reveals a random survival forest (RSF) prognostic model for LUSC. The 12-gene RSF model exhibits high prognostic power in more than 1,000 LUSC patients. High-risk LUSC patients are associated with worse survival and the activation of the epithelial-mesenchymal transition pathway. Additionally, high-risk LUSC patients are resistant to docetaxel or vinorelbine treatment. In vitro and in vivo drug sensitivity experiments indicates that high-risk HCC15/H226 tumour cells and cell line-derived xenograft models are more resistant to vinorelbine treatment. Furthermore, the combination of chemotherapy with transforming growth factor-β inhibition augments antitumour responses in LUSC tumours. Our study provides valuable insights into prognosis stratification and the development of therapeutic strategies for LUSC.https://doi.org/10.1038/s42003-025-07595-x |
| spellingShingle | Liangdong Sun Jue Wang Huansha Yu Xinsheng Zhu Jing Zhang Junjie Hu Yilv Yan Xun Zhang Yuming Zhu Gening Jiang Ming Ding Peng Zhang Lele Zhang Selective inhibition of TGF-β-induced epithelial-mesenchymal transition overcomes chemotherapy resistance in high-risk lung squamous cell carcinoma Communications Biology |
| title | Selective inhibition of TGF-β-induced epithelial-mesenchymal transition overcomes chemotherapy resistance in high-risk lung squamous cell carcinoma |
| title_full | Selective inhibition of TGF-β-induced epithelial-mesenchymal transition overcomes chemotherapy resistance in high-risk lung squamous cell carcinoma |
| title_fullStr | Selective inhibition of TGF-β-induced epithelial-mesenchymal transition overcomes chemotherapy resistance in high-risk lung squamous cell carcinoma |
| title_full_unstemmed | Selective inhibition of TGF-β-induced epithelial-mesenchymal transition overcomes chemotherapy resistance in high-risk lung squamous cell carcinoma |
| title_short | Selective inhibition of TGF-β-induced epithelial-mesenchymal transition overcomes chemotherapy resistance in high-risk lung squamous cell carcinoma |
| title_sort | selective inhibition of tgf β induced epithelial mesenchymal transition overcomes chemotherapy resistance in high risk lung squamous cell carcinoma |
| url | https://doi.org/10.1038/s42003-025-07595-x |
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