Proteomic characterization of esophageal squamous cell carcinoma response to immunotherapy reveals potential therapeutic strategy and predictive biomarkers.

Publisher: Biomed Central Country of Publication: England NLM ID: 101468937 Publication Model: Electronic Cited Medium: Internet ISSN: 1756-8722 (Electronic) Linking ISSN: 17568722 NLM ISO Abbreviation: J Hematol Oncol Subsets: MEDLINE

Original Publication: [London] : Biomed Central, 2008-

Esophageal Squamous Cell Carcinoma*/therapy ; Carcinoma, Squamous Cell*/pathology ; Esophageal Neoplasms*/therapy ; Esophageal Neoplasms*/pathology; Humans ; Proteomics ; Biomarkers ; Immunotherapy

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.
(© 2024. The Author(s).)

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32301236 the Young Scientists Fund of the National Natural Science Foundation of China; 32201215 the Young Scientists Fund of the National Natural Science Foundation of China; 32201212 the Young Scientists Fund of the National Natural Science Foundation of China; 23YF1402800 Shanghai Sailing Program; 22YF1403100 Shanghai Sailing Program; 82003154 National Natural Science Foundation of China; 82372669 National Natural Science Foundation of China; 32330062 National Natural Science Foundation of China; 2022YFA1303200 National Key Research and Development Program of China; 22XD1420100 Program of Shanghai Academic Research Leader; ZJ2019-ZD-004 the Major Project of Special Development Funds of Zhangjiang National Independent Innovation Demonstration Zone; 2017SHZDZX01 the Science and Technology Commission of Shanghai Municipality

Keywords: Anti-PD1 immunotherapy; Esophageal squamous cell carcinoma; Immunotherapy response prediction; Platelets activation; Predictive markers; Proteomics

0 (Biomarkers)

Date Created: 20240316 Date Completed: 20240318 Latest Revision: 20240419

20240419

PMC10943778

10.1186/s13045-024-01534-9

38491392