Scholarlink

Background <p>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.</p> Methods <p>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.</p> Results <p>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.</p> Conclusions <p>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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月8日

查看全文
  • Bastian Grothey,
  • Max Krämer,
  • Matteo Montalbano,
  • Su Ir Lyu,
  • Christiane J. Bruns,
  • Thomas Zander,
  • Reinhard Büttner,
  • Alexander Quaas

摘要

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.