Proteomic characterization of SMARCA-deficient esophageal adenocarcinoma reveals complement evasion and DNA repair-associated prognostic subgroups.

Authors

Bastian Grothey, Max Krämer, Matteo Montalbano, Su Ir Lyu, Christiane J Bruns, Thomas Zander, Reinhard Büttner, Alexander Quaas

Published in

British journal of cancer. Jul 08, 2026. Epub Jul 08, 2026.

Abstract

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.
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.
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.
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.

PMID:
42420628
Bibliographic data and abstract were imported from PubMed on 09 Jul 2026.

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