Optimizing the NGS-based discrimination of multiple lung cancers from the perspective of evolution
Abstract Next-generation sequencing (NGS) offers a promising approach for differentiating multiple primary lung cancers (MPLC) from intrapulmonary metastasis (IPM), though panel selection and clonal interpretation remain challenging. Whole-exome sequencing (WES) data from 80 lung cancer samples were...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | npj Precision Oncology |
| Online Access: | https://doi.org/10.1038/s41698-024-00786-5 |
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| author | Ziyang Wang Xiaoqiu Yuan Kunkun Sun Fang Wu Ke Liu Yiruo Jin Olga Chervova Yuntao Nie Airong Yang Yichen Jin Jing Li Yun Li Fan Yang Jun Wang Stephan Beck David Carbone Guanchao Jiang Kezhong Chen |
| author_facet | Ziyang Wang Xiaoqiu Yuan Kunkun Sun Fang Wu Ke Liu Yiruo Jin Olga Chervova Yuntao Nie Airong Yang Yichen Jin Jing Li Yun Li Fan Yang Jun Wang Stephan Beck David Carbone Guanchao Jiang Kezhong Chen |
| author_sort | Ziyang Wang |
| collection | DOAJ |
| description | Abstract Next-generation sequencing (NGS) offers a promising approach for differentiating multiple primary lung cancers (MPLC) from intrapulmonary metastasis (IPM), though panel selection and clonal interpretation remain challenging. Whole-exome sequencing (WES) data from 80 lung cancer samples were utilized to simulate MPLC and IPM, with various sequenced panels constructed through gene subsampling. Two clonal interpretation approaches primarily applied in clinical practice, MoleA (based on shared mutation comparison) and MoleB (based on probability calculation), were subsequently evaluated. ROC analysis highlighted MoleB’s superior performance, especially with the NCCNplus panel (AUC = 0.950 ± 0.002) and pancancer MoleA (AUC = 0.792 ± 0.004). In two independent cohorts (WES cohort, N = 42 and non-WES cohort, N = 94), NGS-based methodologies effectively stratified disease-free survival, with NCCNplus MoleB further predicting prognosis. Phylogenetic analysis further revealed evolutionary distinctions between MPLC and IPM, establishing an optimized NGS-based framework for differentiating multiple lung cancers. |
| format | Article |
| id | doaj-art-1e10ce7f5a0440478ad2365048dcc802 |
| institution | Kabale University |
| issn | 2397-768X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Precision Oncology |
| spelling | doaj-art-1e10ce7f5a0440478ad2365048dcc8022025-01-19T12:08:14ZengNature Portfolionpj Precision Oncology2397-768X2025-01-019111510.1038/s41698-024-00786-5Optimizing the NGS-based discrimination of multiple lung cancers from the perspective of evolutionZiyang Wang0Xiaoqiu Yuan1Kunkun Sun2Fang Wu3Ke Liu4Yiruo Jin5Olga Chervova6Yuntao Nie7Airong Yang8Yichen Jin9Jing Li10Yun Li11Fan Yang12Jun Wang13Stephan Beck14David Carbone15Guanchao Jiang16Kezhong Chen17Department of Thoracic Surgery, Peking University People’s HospitalDepartment of Thoracic Surgery, Peking University People’s HospitalDepartment of Pathology, Peking University People’s HospitalDepartment of Oncology, The Second Xiangya HospitalBerry Oncology CorporationDepartment of Thoracic Surgery, Peking University People’s HospitalUniversity College London Cancer Institute, University College LondonChina-Japan Friendship HospitalBerry Oncology CorporationDepartment of Thoracic Surgery, Peking University People’s HospitalBerry Oncology CorporationDepartment of Thoracic Surgery, Peking University People’s HospitalDepartment of Thoracic Surgery, Peking University People’s HospitalDepartment of Thoracic Surgery, Peking University People’s HospitalUniversity College London Cancer Institute, University College LondonJames Thoracic Oncology Center, Ohio State UniversityDepartment of Thoracic Surgery, Peking University People’s HospitalDepartment of Thoracic Surgery, Peking University People’s HospitalAbstract Next-generation sequencing (NGS) offers a promising approach for differentiating multiple primary lung cancers (MPLC) from intrapulmonary metastasis (IPM), though panel selection and clonal interpretation remain challenging. Whole-exome sequencing (WES) data from 80 lung cancer samples were utilized to simulate MPLC and IPM, with various sequenced panels constructed through gene subsampling. Two clonal interpretation approaches primarily applied in clinical practice, MoleA (based on shared mutation comparison) and MoleB (based on probability calculation), were subsequently evaluated. ROC analysis highlighted MoleB’s superior performance, especially with the NCCNplus panel (AUC = 0.950 ± 0.002) and pancancer MoleA (AUC = 0.792 ± 0.004). In two independent cohorts (WES cohort, N = 42 and non-WES cohort, N = 94), NGS-based methodologies effectively stratified disease-free survival, with NCCNplus MoleB further predicting prognosis. Phylogenetic analysis further revealed evolutionary distinctions between MPLC and IPM, establishing an optimized NGS-based framework for differentiating multiple lung cancers.https://doi.org/10.1038/s41698-024-00786-5 |
| spellingShingle | Ziyang Wang Xiaoqiu Yuan Kunkun Sun Fang Wu Ke Liu Yiruo Jin Olga Chervova Yuntao Nie Airong Yang Yichen Jin Jing Li Yun Li Fan Yang Jun Wang Stephan Beck David Carbone Guanchao Jiang Kezhong Chen Optimizing the NGS-based discrimination of multiple lung cancers from the perspective of evolution npj Precision Oncology |
| title | Optimizing the NGS-based discrimination of multiple lung cancers from the perspective of evolution |
| title_full | Optimizing the NGS-based discrimination of multiple lung cancers from the perspective of evolution |
| title_fullStr | Optimizing the NGS-based discrimination of multiple lung cancers from the perspective of evolution |
| title_full_unstemmed | Optimizing the NGS-based discrimination of multiple lung cancers from the perspective of evolution |
| title_short | Optimizing the NGS-based discrimination of multiple lung cancers from the perspective of evolution |
| title_sort | optimizing the ngs based discrimination of multiple lung cancers from the perspective of evolution |
| url | https://doi.org/10.1038/s41698-024-00786-5 |
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