Related Experiment Video
Updated: Jul 10, 2026
Development of Compendium for Esophageal Squamous Cell Carcinoma
Published on: April 12, 2024
Proteomic characterization of SMARCA-deficient esophageal adenocarcinoma reveals complement evasion and DNA
Bastian Grothey1, Max Krämer2, Matteo Montalbano3,4
1Institute of Pathology, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany. bastian.grothey@uk-koeln.de.
Background:
Oesophageal adenocarcinoma (EAC) is an aggressive malignancy in which the SWI/SNF catalytic subunits SMARCA2 and SMARCA4 are frequently lost, yet the biological and clinical impact of these deficiencies remains unclear.
Methods:
We analysed 113 EAC specimens using mass spectrometry-based proteomics, including 89 SMARCA-deficient and 24 SMARCA-proficient tumours. Additional immunohistochemical studies were conducted on 98 cases. Differential expression, pathway enrichment, and survival analyses were used to characterise proteomic alterations and identify prognostic features.
Results:
SMARCA-deficient tumours showed frequent expression of complement-inactivating proteins CD55 and CD59 with distinctive apical and membranous localisation. SMARCA4-deficient patients had significantly poorer survival than both SMARCA2-deficient and SMARCA-proficient patients. Among neoadjuvantly treated SMARCA-deficient tumours, coordinated upregulation of DNA repair proteins separated patients into two prognostic subgroups. The DNA repair-low subgroup had markedly worse survival than both the DNA repair-high subgroup and SMARCA-proficient controls, whereas the DNA repair-high subgroup showed a trend toward improved outcomes. This DNA repair-associated pattern was not observed in neoadjuvantly treated SMARCA-proficient tumours.
Conclusions:
SMARCA-deficient EAC comprises biologically distinct subgroups with prognostic proteomic signatures. CD55 and CD59 expression may contribute to resistance to antibody-based immunotherapies by complement evasion, while DNA repair profiles could guide post-surgical treatment in neoadjuvantly treated patients.
Insights
Loss of SMARCA2/SMARCA4 in oesophageal adenocarcinoma creates distinct subgroups. These subgroups have unique proteomic signatures, impacting survival and potential treatment responses, particularly with immunotherapies and DNA repair pathways.
Area of Science:
- Oncology
- Molecular Biology
- Proteomics
Background:
- Oesophageal adenocarcinoma (EAC) is an aggressive cancer.
- Loss of SWI/SNF subunits SMARCA2 and SMARCA4 is common in EAC.
- The clinical and biological impact of these genetic losses is not well understood.
Purpose of the Study:
- To investigate the proteomic differences in SMARCA-deficient EAC.
- To identify potential prognostic biomarkers and therapeutic targets.
Main Methods:
- Proteomic analysis using mass spectrometry on 113 EAC specimens (89 SMARCA-deficient, 24 SMARCA-proficient).
- Immunohistochemical studies on 98 cases.
- Differential expression, pathway enrichment, and survival analyses.
Main Results:
- SMARCA-deficient tumors showed increased expression of CD55 and CD59.
- SMARCA4-deficient patients had significantly worse survival.
- Upregulation of DNA repair proteins in neoadjuvantly treated SMARCA-deficient tumors identified distinct prognostic subgroups.
Conclusions:
- SMARCA-deficient EAC presents biologically distinct subgroups with prognostic proteomic signatures.
- CD55 and CD59 expression may confer resistance to antibody-based immunotherapies via complement evasion.
- DNA repair profiles could inform post-surgical treatment strategies for neoadjuvantly treated patients.
Related Concept Videos
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...