Scholarlink

Background <p>The epithelial-mesenchymal axis frames gastric cancer heterogeneity but mainly captures phenotypic extremes. CCNE1 gain, encompassing amplification or Cyclin E1 overexpression, represents one intermediate state linked to chromosomal instability and therapeutic resistance. However, its clinicopathologic identity and immune features in gastric cancer remain insufficiently characterised.</p> Methods <p>We analysed 1273 gastric cancer patients across six independent cohorts: ZSHS (<i>n</i> = 453), TCGA (<i>n</i> = 410), ACRG (<i>n</i> = 300), SMC (<i>n</i> = 43), MSKCC (<i>n</i> = 22), and ZSHS NGS cohort (<i>n</i> = 45). Tumours were classified into CCNE1 gain, epithelial, or mesenchymal subtypes using protein, copy-number, or transcript-level data. Clinicopathologic features, survival outcomes, treatment responses, and immune contexture were evaluated across subtypes.</p> Results <p>CCNE1 gain tumours retained E-cadherin positivity but showed increased proliferation, more nerve and venous invasion. They were associated with poor prognosis and reduced response to adjuvant chemotherapy, HER2-targeted therapy, anti-angiogenic agents, and PD-1 blockade independent of epithelial-mesenchymal classification. The immune contexture exhibited an immune-desert phenotype with reduced lymphocyte infiltration, impaired cytotoxicity, increased M2 macrophage polarisation, and elevated TGF-β.</p> Conclusion <p>CCNE1 gain delineates a clinic-ready, therapy-refractory subtype of gastric cancer beyond the epithelial-mesenchymal framework, representing over one in ten patients. These tumours preserve epithelial morphology yet exhibit aggressive proliferative and invasive behaviour, coupled with immune desert and myeloid-driven suppression.</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

Lethal clinical outcome and immune desert contexture in refractory gastric cancer harboring CCNE1 amplification and overexpression

  • 期刊论文

  • 发表日期：

    2026年4月28日

查看全文
  • Yun Gu,
  • Jieti Wang,
  • Zhen Ling,
  • Jingquan Liu,
  • Chao Lin,
  • Hao Liu,
  • Hongyong He,
  • Ruochen Li,
  • Shao Fei,
  • Jiejie Xu

摘要

Background

The epithelial-mesenchymal axis frames gastric cancer heterogeneity but mainly captures phenotypic extremes. CCNE1 gain, encompassing amplification or Cyclin E1 overexpression, represents one intermediate state linked to chromosomal instability and therapeutic resistance. However, its clinicopathologic identity and immune features in gastric cancer remain insufficiently characterised.

Methods

We analysed 1273 gastric cancer patients across six independent cohorts: ZSHS (n = 453), TCGA (n = 410), ACRG (n = 300), SMC (n = 43), MSKCC (n = 22), and ZSHS NGS cohort (n = 45). Tumours were classified into CCNE1 gain, epithelial, or mesenchymal subtypes using protein, copy-number, or transcript-level data. Clinicopathologic features, survival outcomes, treatment responses, and immune contexture were evaluated across subtypes.

Results

CCNE1 gain tumours retained E-cadherin positivity but showed increased proliferation, more nerve and venous invasion. They were associated with poor prognosis and reduced response to adjuvant chemotherapy, HER2-targeted therapy, anti-angiogenic agents, and PD-1 blockade independent of epithelial-mesenchymal classification. The immune contexture exhibited an immune-desert phenotype with reduced lymphocyte infiltration, impaired cytotoxicity, increased M2 macrophage polarisation, and elevated TGF-β.

Conclusion

CCNE1 gain delineates a clinic-ready, therapy-refractory subtype of gastric cancer beyond the epithelial-mesenchymal framework, representing over one in ten patients. These tumours preserve epithelial morphology yet exhibit aggressive proliferative and invasive behaviour, coupled with immune desert and myeloid-driven suppression.