Proteogenomic Characterization of High-Grade Lung Neuroendocrine Carcinoma Deciphers Molecular Diversity and Potential Biomarkers of Different Histological Subtypes in Chinese Population
High-grade lung neuroendocrine carcinomas (Lu-NECs) are clinically refractory malignancies with poor prognosis and limited therapeutic advances. The biological and molecular features underlying the histological heterogeneity of Lu-NECs are not fully understood. In this study, we present a multi-omic...
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| Format: | Article |
| Language: | English |
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American Association for the Advancement of Science (AAAS)
2025-01-01
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| Series: | Research |
| Online Access: | https://spj.science.org/doi/10.34133/research.0671 |
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| author | Zicheng Zhang Xi Wu Siqi Bao Xujie Sun Fan Yang Yibo Zhang Zijian Yang Liujin Zhang Ruanqi Chen Puyuan Xing Junling Li Meng Zhou Lin Yang |
| author_facet | Zicheng Zhang Xi Wu Siqi Bao Xujie Sun Fan Yang Yibo Zhang Zijian Yang Liujin Zhang Ruanqi Chen Puyuan Xing Junling Li Meng Zhou Lin Yang |
| author_sort | Zicheng Zhang |
| collection | DOAJ |
| description | High-grade lung neuroendocrine carcinomas (Lu-NECs) are clinically refractory malignancies with poor prognosis and limited therapeutic advances. The biological and molecular features underlying the histological heterogeneity of Lu-NECs are not fully understood. In this study, we present a multi-omics integration of whole-exome sequencing and deep proteomic profiling in 93 Chinese Lu-NECs to establish the first comprehensive proteogenomic atlas of this disease spectrum. Our analyses revealed a high degree of mutational concordance among the subtypes at the genomic level; however, distinct proteomic profiles enabled a clear differentiation of histological subtypes, unveiling subtype-specific molecular and biological features related to tumor metabolism, immunity, and proliferation. Furthermore, RB1 mutations confer divergent prognostic effects through subtype-specific cis- and trans-proteomic regulation. In addition, we identified potential protein biomarkers for histological subtype classification and risk stratification, which were validated by immunohistochemistry in an independent cohort. This study provides a valuable proteogenomic resource and insight into Lu-NEC heterogeneity. |
| format | Article |
| id | doaj-art-df8a660247ee4897aefa2c9c8a0f14c5 |
| institution | OA Journals |
| issn | 2639-5274 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | Article |
| series | Research |
| spelling | doaj-art-df8a660247ee4897aefa2c9c8a0f14c52025-08-20T02:12:07ZengAmerican Association for the Advancement of Science (AAAS)Research2639-52742025-01-01810.34133/research.0671Proteogenomic Characterization of High-Grade Lung Neuroendocrine Carcinoma Deciphers Molecular Diversity and Potential Biomarkers of Different Histological Subtypes in Chinese PopulationZicheng Zhang0Xi Wu1Siqi Bao2Xujie Sun3Fan Yang4Yibo Zhang5Zijian Yang6Liujin Zhang7Ruanqi Chen8Puyuan Xing9Junling Li10Meng Zhou11Lin Yang12School of Biomedical Engineering, Wenzhou Medical University, Wenzhou 325027, P. R. China.Department of Comprehensive Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P. R. China.School of Biomedical Engineering, Wenzhou Medical University, Wenzhou 325027, P. R. China.Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P. R. China.Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P. R. China.School of Biomedical Engineering, Wenzhou Medical University, Wenzhou 325027, P. R. China.School of Biomedical Engineering, Wenzhou Medical University, Wenzhou 325027, P. R. China.School of Biomedical Engineering, Wenzhou Medical University, Wenzhou 325027, P. R. China.Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P. R. China.Department of Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P. R. China.Department of Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P. R. China.School of Biomedical Engineering, Wenzhou Medical University, Wenzhou 325027, P. R. China.Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P. R. China.High-grade lung neuroendocrine carcinomas (Lu-NECs) are clinically refractory malignancies with poor prognosis and limited therapeutic advances. The biological and molecular features underlying the histological heterogeneity of Lu-NECs are not fully understood. In this study, we present a multi-omics integration of whole-exome sequencing and deep proteomic profiling in 93 Chinese Lu-NECs to establish the first comprehensive proteogenomic atlas of this disease spectrum. Our analyses revealed a high degree of mutational concordance among the subtypes at the genomic level; however, distinct proteomic profiles enabled a clear differentiation of histological subtypes, unveiling subtype-specific molecular and biological features related to tumor metabolism, immunity, and proliferation. Furthermore, RB1 mutations confer divergent prognostic effects through subtype-specific cis- and trans-proteomic regulation. In addition, we identified potential protein biomarkers for histological subtype classification and risk stratification, which were validated by immunohistochemistry in an independent cohort. This study provides a valuable proteogenomic resource and insight into Lu-NEC heterogeneity.https://spj.science.org/doi/10.34133/research.0671 |
| spellingShingle | Zicheng Zhang Xi Wu Siqi Bao Xujie Sun Fan Yang Yibo Zhang Zijian Yang Liujin Zhang Ruanqi Chen Puyuan Xing Junling Li Meng Zhou Lin Yang Proteogenomic Characterization of High-Grade Lung Neuroendocrine Carcinoma Deciphers Molecular Diversity and Potential Biomarkers of Different Histological Subtypes in Chinese Population Research |
| title | Proteogenomic Characterization of High-Grade Lung Neuroendocrine Carcinoma Deciphers Molecular Diversity and Potential Biomarkers of Different Histological Subtypes in Chinese Population |
| title_full | Proteogenomic Characterization of High-Grade Lung Neuroendocrine Carcinoma Deciphers Molecular Diversity and Potential Biomarkers of Different Histological Subtypes in Chinese Population |
| title_fullStr | Proteogenomic Characterization of High-Grade Lung Neuroendocrine Carcinoma Deciphers Molecular Diversity and Potential Biomarkers of Different Histological Subtypes in Chinese Population |
| title_full_unstemmed | Proteogenomic Characterization of High-Grade Lung Neuroendocrine Carcinoma Deciphers Molecular Diversity and Potential Biomarkers of Different Histological Subtypes in Chinese Population |
| title_short | Proteogenomic Characterization of High-Grade Lung Neuroendocrine Carcinoma Deciphers Molecular Diversity and Potential Biomarkers of Different Histological Subtypes in Chinese Population |
| title_sort | proteogenomic characterization of high grade lung neuroendocrine carcinoma deciphers molecular diversity and potential biomarkers of different histological subtypes in chinese population |
| url | https://spj.science.org/doi/10.34133/research.0671 |
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