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Dissecting small cell carcinoma of the esophagus ecosystem by single-cell transcriptomic analysis
Hao-Xiang Wu1,2,3,4, Yu-Kun Chen1,2,5,4, Ying-Nan Wang1,2,4
1Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China.
Molecular Cancer
|May 15, 2025
Summary
This study reveals that small cell carcinoma of the esophagus (SCCE) has an immune-suppressive tumor microenvironment (TME) and epithelial heterogeneity. SCCE patients may benefit from anti-angiogenesis therapy.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Small cell carcinoma of the esophagus (SCCE) is a rare, aggressive neuroendocrine cancer with a poor prognosis.
- Understanding the tumor microenvironment (TME) and epithelial heterogeneity is crucial for developing effective treatments.
Purpose of the Study:
- To comprehensively analyze the TME and epithelial landscape of SCCE using single-cell transcriptional profiling.
- To identify potential therapeutic targets and biomarkers for SCCE.
Main Methods:
- Single-cell RNA sequencing was performed on tumor samples from 10 SCCE patients.
- Normal esophageal mucosa, adjacent non-malignant tissue, and esophageal squamous cell carcinoma (ESCC) were used as references.
- Analysis included TME ecotype identification and transcriptional metaprogram construction.
Main Results:
- SCCE exhibits an immune-suppressive TME with activated regulatory T cells and an angiogenesis-induced niche, distinct from ESCC.
- Five TME ecotypes were identified, with EC1 being enriched in SCCE and associated with molecular subtypes and survival.
- Eight transcriptional metaprograms highlighted significant epithelial heterogeneity in SCCE, with MP5 linked to neuroendocrine phenotype and poor survival.
Conclusions:
- This study provides the first systematic deciphering of SCCE's TME and epithelial heterogeneity.
- Findings suggest SCCE patients could potentially benefit from anti-angiogenesis therapies.
