Single-cell analysis reveals transcriptomic features and therapeutic targets in primary pulmonary lymphoepithelioma-like carcinoma
Abstract Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is a rare subtype of non-small-cell lung cancer. Duo to the current lack of precise targeted therapies, there is an urgent need to identify novel therapeutic targets. In this study, we perform single-nucleus transcriptome analysis...
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| Format: | Article |
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Nature Portfolio
2025-03-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07819-0 |
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| author | Binghua Tan Ke Xu Yingcheng Lyu Yicheng Liang Ruihao Liang Kai Lei Jialu Liang Jing Huang Kefeng Wang Duoguang Wu Wenjian Wang Xueting Hu Kexi Wang Minghui Wang Huayue Lin |
| author_facet | Binghua Tan Ke Xu Yingcheng Lyu Yicheng Liang Ruihao Liang Kai Lei Jialu Liang Jing Huang Kefeng Wang Duoguang Wu Wenjian Wang Xueting Hu Kexi Wang Minghui Wang Huayue Lin |
| author_sort | Binghua Tan |
| collection | DOAJ |
| description | Abstract Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is a rare subtype of non-small-cell lung cancer. Duo to the current lack of precise targeted therapies, there is an urgent need to identify novel therapeutic targets. In this study, we perform single-nucleus transcriptome analysis on PPLELC samples to reveal the molecular tumor heterogeneity and characterize the functional states of immune cells within the tumor microenvironment. We identify a critical malignant subpopulation of PPLELC characterized by elevated expression of AKT3 and FGFR2. Higher expression levels of AKT3 and FGFR2 are associated with poorer patient outcomes. Moreover, treatment with either an AKT3 inhibitor or an FGFR2 inhibitor significantly attenuates tumor progression in patient-derived xenograft models. Our findings highlight AKT3 and FGFR2 as potential therapeutic targets and prognostic biomarkers, providing valuable insights for the development of rational targeted therapies and immunotherapeutic strategies. |
| format | Article |
| id | doaj-art-18a2b172d69a46099aea7d7ab8e0bad6 |
| institution | DOAJ |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-18a2b172d69a46099aea7d7ab8e0bad62025-08-20T03:05:46ZengNature PortfolioCommunications Biology2399-36422025-03-018111410.1038/s42003-025-07819-0Single-cell analysis reveals transcriptomic features and therapeutic targets in primary pulmonary lymphoepithelioma-like carcinomaBinghua Tan0Ke Xu1Yingcheng Lyu2Yicheng Liang3Ruihao Liang4Kai Lei5Jialu Liang6Jing Huang7Kefeng Wang8Duoguang Wu9Wenjian Wang10Xueting Hu11Kexi Wang12Minghui Wang13Huayue Lin14Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityAbstract Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is a rare subtype of non-small-cell lung cancer. Duo to the current lack of precise targeted therapies, there is an urgent need to identify novel therapeutic targets. In this study, we perform single-nucleus transcriptome analysis on PPLELC samples to reveal the molecular tumor heterogeneity and characterize the functional states of immune cells within the tumor microenvironment. We identify a critical malignant subpopulation of PPLELC characterized by elevated expression of AKT3 and FGFR2. Higher expression levels of AKT3 and FGFR2 are associated with poorer patient outcomes. Moreover, treatment with either an AKT3 inhibitor or an FGFR2 inhibitor significantly attenuates tumor progression in patient-derived xenograft models. Our findings highlight AKT3 and FGFR2 as potential therapeutic targets and prognostic biomarkers, providing valuable insights for the development of rational targeted therapies and immunotherapeutic strategies.https://doi.org/10.1038/s42003-025-07819-0 |
| spellingShingle | Binghua Tan Ke Xu Yingcheng Lyu Yicheng Liang Ruihao Liang Kai Lei Jialu Liang Jing Huang Kefeng Wang Duoguang Wu Wenjian Wang Xueting Hu Kexi Wang Minghui Wang Huayue Lin Single-cell analysis reveals transcriptomic features and therapeutic targets in primary pulmonary lymphoepithelioma-like carcinoma Communications Biology |
| title | Single-cell analysis reveals transcriptomic features and therapeutic targets in primary pulmonary lymphoepithelioma-like carcinoma |
| title_full | Single-cell analysis reveals transcriptomic features and therapeutic targets in primary pulmonary lymphoepithelioma-like carcinoma |
| title_fullStr | Single-cell analysis reveals transcriptomic features and therapeutic targets in primary pulmonary lymphoepithelioma-like carcinoma |
| title_full_unstemmed | Single-cell analysis reveals transcriptomic features and therapeutic targets in primary pulmonary lymphoepithelioma-like carcinoma |
| title_short | Single-cell analysis reveals transcriptomic features and therapeutic targets in primary pulmonary lymphoepithelioma-like carcinoma |
| title_sort | single cell analysis reveals transcriptomic features and therapeutic targets in primary pulmonary lymphoepithelioma like carcinoma |
| url | https://doi.org/10.1038/s42003-025-07819-0 |
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