Proteomic characterization of esophageal squamous cell carcinoma response to immunotherapy reveals potential therapeutic strategy and predictive biomarkers
Abstract Immunotherapy is the first-line therapy for esophageal squamous cell carcinoma (ESCC), yet many patients do not respond due to drug resistance and the lack of reliable predictive markers. We collected 73 ESCC patients (including discovery cohort and validation cohort) without immune thrombo...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-03-01
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| Series: | Journal of Hematology & Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13045-024-01534-9 |
| _version_ | 1827315850975117312 |
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| author | Fahan Ma Yan Li Chan Xiang Bing Wang Jie Lv Jinzhi Wei Zhaoyu Qin Yan Pu Kai Li Haohua Teng Subei Tan Jinwen Feng Zhanxian Shang Yunzhi Wang Sha Tian Changsheng Du Yuchen Han Chen Ding |
| author_facet | Fahan Ma Yan Li Chan Xiang Bing Wang Jie Lv Jinzhi Wei Zhaoyu Qin Yan Pu Kai Li Haohua Teng Subei Tan Jinwen Feng Zhanxian Shang Yunzhi Wang Sha Tian Changsheng Du Yuchen Han Chen Ding |
| author_sort | Fahan Ma |
| collection | DOAJ |
| description | Abstract Immunotherapy is the first-line therapy for esophageal squamous cell carcinoma (ESCC), yet many patients do not respond due to drug resistance and the lack of reliable predictive markers. We collected 73 ESCC patients (including discovery cohort and validation cohort) without immune thrombocytopenia and undergoing anti-PD1 immunotherapy. Proteomic and phosphoproteomic analysis of 73 ESCC treatment-naive samples by mass spectrometry-based label-free quantification were applied to explore the potential resistant and sensitive mechanisms, and identify predictive markers of ESCC immunotherapy. Comparative analysis found the pathways related to immune and mitochondrial functions were associated with ESCC immunotherapy sensitivity; while platelet activation bioprocess showed negative correlation with CD8+ T cells and related to ESCC immunotherapy non-sensitivity. Finally, we identified 10 ESCC immunotherapy predictive biomarkers with high accuracy (≥ 0.90) to predict the immunotherapeutic response, which was validated in the independent cohort. |
| first_indexed | 2024-04-24T23:03:57Z |
| format | Article |
| id | doaj.art-aa45ff60bd914b3cabb968bd0e513c9c |
| institution | Directory Open Access Journal |
| issn | 1756-8722 |
| language | English |
| last_indexed | 2024-04-24T23:03:57Z |
| publishDate | 2024-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Hematology & Oncology |
| spelling | doaj.art-aa45ff60bd914b3cabb968bd0e513c9c2024-03-17T12:35:47ZengBMCJournal of Hematology & Oncology1756-87222024-03-011711510.1186/s13045-024-01534-9Proteomic characterization of esophageal squamous cell carcinoma response to immunotherapy reveals potential therapeutic strategy and predictive biomarkersFahan Ma0Yan Li1Chan Xiang2Bing Wang3Jie Lv4Jinzhi Wei5Zhaoyu Qin6Yan Pu7Kai Li8Haohua Teng9Subei Tan10Jinwen Feng11Zhanxian Shang12Yunzhi Wang13Sha Tian14Changsheng Du15Yuchen Han16Chen Ding17State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institutes of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan UniversityState Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institutes of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan UniversityDepartment of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of MedicineState Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institutes of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan UniversityKey Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Life Sciences and Technology, Tongji UniversityDepartment of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of MedicineState Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institutes of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan UniversityState Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institutes of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan UniversityState Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institutes of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan UniversityDepartment of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of MedicineState Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institutes of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan UniversityState Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institutes of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan UniversityDepartment of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of MedicineState Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institutes of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan UniversityState Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institutes of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan UniversityKey Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Life Sciences and Technology, Tongji UniversityDepartment of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of MedicineState Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institutes of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan UniversityAbstract Immunotherapy is the first-line therapy for esophageal squamous cell carcinoma (ESCC), yet many patients do not respond due to drug resistance and the lack of reliable predictive markers. We collected 73 ESCC patients (including discovery cohort and validation cohort) without immune thrombocytopenia and undergoing anti-PD1 immunotherapy. Proteomic and phosphoproteomic analysis of 73 ESCC treatment-naive samples by mass spectrometry-based label-free quantification were applied to explore the potential resistant and sensitive mechanisms, and identify predictive markers of ESCC immunotherapy. Comparative analysis found the pathways related to immune and mitochondrial functions were associated with ESCC immunotherapy sensitivity; while platelet activation bioprocess showed negative correlation with CD8+ T cells and related to ESCC immunotherapy non-sensitivity. Finally, we identified 10 ESCC immunotherapy predictive biomarkers with high accuracy (≥ 0.90) to predict the immunotherapeutic response, which was validated in the independent cohort.https://doi.org/10.1186/s13045-024-01534-9Esophageal squamous cell carcinomaProteomicsAnti-PD1 immunotherapyPlatelets activationPredictive markersImmunotherapy response prediction |
| spellingShingle | Fahan Ma Yan Li Chan Xiang Bing Wang Jie Lv Jinzhi Wei Zhaoyu Qin Yan Pu Kai Li Haohua Teng Subei Tan Jinwen Feng Zhanxian Shang Yunzhi Wang Sha Tian Changsheng Du Yuchen Han Chen Ding Proteomic characterization of esophageal squamous cell carcinoma response to immunotherapy reveals potential therapeutic strategy and predictive biomarkers Journal of Hematology & Oncology Esophageal squamous cell carcinoma Proteomics Anti-PD1 immunotherapy Platelets activation Predictive markers Immunotherapy response prediction |
| title | Proteomic characterization of esophageal squamous cell carcinoma response to immunotherapy reveals potential therapeutic strategy and predictive biomarkers |
| title_full | Proteomic characterization of esophageal squamous cell carcinoma response to immunotherapy reveals potential therapeutic strategy and predictive biomarkers |
| title_fullStr | Proteomic characterization of esophageal squamous cell carcinoma response to immunotherapy reveals potential therapeutic strategy and predictive biomarkers |
| title_full_unstemmed | Proteomic characterization of esophageal squamous cell carcinoma response to immunotherapy reveals potential therapeutic strategy and predictive biomarkers |
| title_short | Proteomic characterization of esophageal squamous cell carcinoma response to immunotherapy reveals potential therapeutic strategy and predictive biomarkers |
| title_sort | proteomic characterization of esophageal squamous cell carcinoma response to immunotherapy reveals potential therapeutic strategy and predictive biomarkers |
| topic | Esophageal squamous cell carcinoma Proteomics Anti-PD1 immunotherapy Platelets activation Predictive markers Immunotherapy response prediction |
| url | https://doi.org/10.1186/s13045-024-01534-9 |
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