This repository contains all analysis code and processed data supporting the above publication. Esophageal adenocarcinoma (EAC) is an aggressive gastrointestinal malignancy with poor prognosis despite multimodal treatment. The SWI/SNF chromatin remodeling complex subunits SMARCA2 (BRM) and SMARCA4 (BRG1) are among the most commonly altered proteins in human cancers, yet their functional and clinical impact in EAC remains poorly understood. In this study, we performed mass spectrometry-based proteomics on 113 EAC specimens — including 89 SMARCA-deficient and 24 SMARCA-proficient tumors — complemented by immunohistochemical analyses of 98 cases. We identified frequent expression of the complement-inactivating proteins CD55 and CD59 in SMARCA-deficient tumors, with distinctive apical and membranous localization suggesting a potential complement evasion mechanism relevant to antibody-based immunotherapy resistance. SMARCA4-deficient patients showed significantly worse survival than both SMARCA2-deficient and SMARCA-proficient patients. Among neoadjuvantly treated SMARCA-deficient cases, coordinated upregulation of DNA repair proteins defined two prognostic subgroups with markedly different outcomes, a pattern absent in SMARCA-proficient controls. This repository provides the preprocessed mass spectrometry data, clinical annotation, immunohistochemistry data, and the complete R analysis pipeline to reproduce all results, figures, and tables reported in the manuscript.
Grothey et al. (Sun,) studied this question.