Molecular characterization of EBV-associated primary pulmonary lymphoepithelial carcinoma by multiomics analysis
Abstract Background Primary pulmonary lymphoepithelial carcinoma (pLEC) is a subtype of non-small cell lung cancer (NSCLC) characterized by Epstein-Barr virus (EBV) infection. However, the molecular pathogenesis of pLEC remains poorly understood. Methods In this study, we explored pLEC using whole-e...
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BMC
2025-01-01
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| Online Access: | https://doi.org/10.1186/s12885-024-13410-3 |
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| author | Meiling Yang Guixian Zheng Fukun Chen Haijuan Tang Yaoyao Liu Xuan Gao Yu Huang Zili Lv Benhua Li Maolin Yang Qing Bu Lixia Zhu Pengli Yu Zengyu Huo Xinyan Wei Xiaoli Chen Yanbing Huang Zhiyi He Xuefeng Xia Jing Bai |
| author_facet | Meiling Yang Guixian Zheng Fukun Chen Haijuan Tang Yaoyao Liu Xuan Gao Yu Huang Zili Lv Benhua Li Maolin Yang Qing Bu Lixia Zhu Pengli Yu Zengyu Huo Xinyan Wei Xiaoli Chen Yanbing Huang Zhiyi He Xuefeng Xia Jing Bai |
| author_sort | Meiling Yang |
| collection | DOAJ |
| description | Abstract Background Primary pulmonary lymphoepithelial carcinoma (pLEC) is a subtype of non-small cell lung cancer (NSCLC) characterized by Epstein-Barr virus (EBV) infection. However, the molecular pathogenesis of pLEC remains poorly understood. Methods In this study, we explored pLEC using whole-exome sequencing (WES) and RNA-whole-transcriptome sequencing (RNA-seq) technologies. Datasets of normal lung tissue, other types of NSCLC, and EBV-positive nasopharyngeal carcinoma (EBV+-NPC) were obtained from public databases. Furthermore, we described the gene signatures, viral integration, cell quantification, cell death and immune infiltration of pLEC. Results Compared with other types of NSCLC and EBV+-NPC, pLEC patients exhibited a lower somatic mutation burden and extensive copy number deletions, including 1p36.23, 3p21.1, 7q11.23, and 11q23.3. Integration of EBV associated dysregulation of gene expression, with CNV-altered regions coinciding with EBV integration sites. Specifically, ZBTB16 and ERRFI1 were downregulated by CNV loss, and the FOXD family genes were overexpressed with CNV gain. Decreased expression of the FOXD family might be associated with a favorable prognosis in pLEC patients, and these patients exhibited enhanced cytotoxicity. Conclusion Compared with other types of NSCLC and NPC, pLEC has distinct molecular characteristics. EBV integration, the aberrant expression of genes, as well as the loss of CNVs, may play a crucial role in the pathogenesis of pLEC. However, further research is needed to assess the potential role of the FOXD gene family as a biomarker. |
| format | Article |
| id | doaj-art-3e29758388114a94ad71d536d9bfcb94 |
| institution | Kabale University |
| issn | 1471-2407 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj-art-3e29758388114a94ad71d536d9bfcb942025-01-19T12:26:56ZengBMCBMC Cancer1471-24072025-01-0125111710.1186/s12885-024-13410-3Molecular characterization of EBV-associated primary pulmonary lymphoepithelial carcinoma by multiomics analysisMeiling Yang0Guixian Zheng1Fukun Chen2Haijuan Tang3Yaoyao Liu4Xuan Gao5Yu Huang6Zili Lv7Benhua Li8Maolin Yang9Qing Bu10Lixia Zhu11Pengli Yu12Zengyu Huo13Xinyan Wei14Xiaoli Chen15Yanbing Huang16Zhiyi He17Xuefeng Xia18Jing Bai19Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical UniversityGeneplus-Beijing InstituteDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical UniversityGeneplus-Beijing InstituteGeneplus-Beijing InstituteDepartment of Medical Oncology, Affiliated Tumor Hospital of Guangxi Medical UniversityDepartment of Pathology, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Medical Oncology, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical UniversityGeneplus-Beijing InstituteDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical UniversityGeneplus-Beijing InstituteDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical UniversityAbstract Background Primary pulmonary lymphoepithelial carcinoma (pLEC) is a subtype of non-small cell lung cancer (NSCLC) characterized by Epstein-Barr virus (EBV) infection. However, the molecular pathogenesis of pLEC remains poorly understood. Methods In this study, we explored pLEC using whole-exome sequencing (WES) and RNA-whole-transcriptome sequencing (RNA-seq) technologies. Datasets of normal lung tissue, other types of NSCLC, and EBV-positive nasopharyngeal carcinoma (EBV+-NPC) were obtained from public databases. Furthermore, we described the gene signatures, viral integration, cell quantification, cell death and immune infiltration of pLEC. Results Compared with other types of NSCLC and EBV+-NPC, pLEC patients exhibited a lower somatic mutation burden and extensive copy number deletions, including 1p36.23, 3p21.1, 7q11.23, and 11q23.3. Integration of EBV associated dysregulation of gene expression, with CNV-altered regions coinciding with EBV integration sites. Specifically, ZBTB16 and ERRFI1 were downregulated by CNV loss, and the FOXD family genes were overexpressed with CNV gain. Decreased expression of the FOXD family might be associated with a favorable prognosis in pLEC patients, and these patients exhibited enhanced cytotoxicity. Conclusion Compared with other types of NSCLC and NPC, pLEC has distinct molecular characteristics. EBV integration, the aberrant expression of genes, as well as the loss of CNVs, may play a crucial role in the pathogenesis of pLEC. However, further research is needed to assess the potential role of the FOXD gene family as a biomarker.https://doi.org/10.1186/s12885-024-13410-3Lung cancerMultiomicsEBVTumor microenvironmentBiomarker |
| spellingShingle | Meiling Yang Guixian Zheng Fukun Chen Haijuan Tang Yaoyao Liu Xuan Gao Yu Huang Zili Lv Benhua Li Maolin Yang Qing Bu Lixia Zhu Pengli Yu Zengyu Huo Xinyan Wei Xiaoli Chen Yanbing Huang Zhiyi He Xuefeng Xia Jing Bai Molecular characterization of EBV-associated primary pulmonary lymphoepithelial carcinoma by multiomics analysis BMC Cancer Lung cancer Multiomics EBV Tumor microenvironment Biomarker |
| title | Molecular characterization of EBV-associated primary pulmonary lymphoepithelial carcinoma by multiomics analysis |
| title_full | Molecular characterization of EBV-associated primary pulmonary lymphoepithelial carcinoma by multiomics analysis |
| title_fullStr | Molecular characterization of EBV-associated primary pulmonary lymphoepithelial carcinoma by multiomics analysis |
| title_full_unstemmed | Molecular characterization of EBV-associated primary pulmonary lymphoepithelial carcinoma by multiomics analysis |
| title_short | Molecular characterization of EBV-associated primary pulmonary lymphoepithelial carcinoma by multiomics analysis |
| title_sort | molecular characterization of ebv associated primary pulmonary lymphoepithelial carcinoma by multiomics analysis |
| topic | Lung cancer Multiomics EBV Tumor microenvironment Biomarker |
| url | https://doi.org/10.1186/s12885-024-13410-3 |
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