Dissecting small cell carcinoma of the esophagus ecosystem by single-cell transcriptomic analysis

IF 27.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Cancer Pub Date : 2025-05-15 DOI:10.1186/s12943-025-02335-5

Hao-Xiang Wu, Yu-Kun Chen, Ying-Nan Wang, Jia-Ying Chen, Shu-Jing Xiang, Ying Jin, Zi-Xian Wang, Chun-Yu Huang, Lu-Ping Yang, Ye He, Wen-Long Guan, Long Bai, Yan-Xing Chen, Min Wang, Chao-Ye Wang, Run-Jie Huang, Yue Huang, Jin-Ling Zhang, Zhi-Da Lv, Si-Qi Yang, Rui-Hua Xu, Qi Zhao, Feng Wang

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Abstract

Small cell carcinoma of the esophagus (SCCE) is an aggressive and rare neuroendocrine malignancy with poor prognosis. Here, we firstly performed single-cell transcriptional profiling derived from 10 SCCE patients, with normal esophageal mucosa, adjacent non-malignant tissue and tumors from esophageal squamous cell carcinoma (ESCC) as reference. We observed enrichment of activated regulatory T cells and an angiogenesis-induced niche existed in SCCE compared with ESCC, revealing an immune suppressive and vessel-induced tumor microenvironment (TME) in SCCE. Totally, we identified five TME ecotypes (EC1 ~ 5). Notably, EC1 was highly enriched in SCCE, associating with molecular subtyping and survival outcomes. To dissecting heterogeneity of epithelium in SCCE, we constructed eight transcriptional metaprograms (MPs) that underscored significant heterogeneity of SCCE. High expression of MP5 was linked to neuroendocrine phenotype and poor clinical survival. Collectively, these results, for the first time, systematically deciphered the TME and epithelial heterogeneity of SCCE and provided evidences that SCCE patients might benefit from anti-angiogenesis therapy.

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单细胞转录组学分析食管小细胞癌生态系统

食道小细胞癌是一种侵袭性、罕见的神经内分泌恶性肿瘤，预后较差。在这里，我们首先对10例SCCE患者进行了单细胞转录谱分析，以正常食管黏膜、邻近非恶性组织和食管鳞状细胞癌（ESCC）肿瘤为对照。与ESCC相比，我们观察到SCCE中活化的调节性T细胞的富集和血管生成诱导的生态位，揭示了SCCE中免疫抑制和血管诱导的肿瘤微环境（TME）。共鉴定出5种TME生态型（EC1 ~ 5）。值得注意的是，EC1在SCCE中高度富集，与分子分型和生存结果相关。为了剖析SCCE中上皮的异质性，我们构建了8个转录元程序（MPs）来强调SCCE的显著异质性。MP5的高表达与神经内分泌表型和较差的临床生存率有关。总的来说，这些结果首次系统地揭示了SCCE的TME和上皮异质性，并为SCCE患者可能受益于抗血管生成治疗提供了证据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Cancer 医学-生化与分子生物学

CiteScore

54.90

自引率

2.70%

发文量

224

审稿时长

2 months

期刊介绍： Molecular Cancer is a platform that encourages the exchange of ideas and discoveries in the field of cancer research, particularly focusing on the molecular aspects. Our goal is to facilitate discussions and provide insights into various areas of cancer and related biomedical science. We welcome articles from basic, translational, and clinical research that contribute to the advancement of understanding, prevention, diagnosis, and treatment of cancer. The scope of topics covered in Molecular Cancer is diverse and inclusive. These include, but are not limited to, cell and tumor biology, angiogenesis, utilizing animal models, understanding metastasis, exploring cancer antigens and the immune response, investigating cellular signaling and molecular biology, examining epidemiology, genetic and molecular profiling of cancer, identifying molecular targets, studying cancer stem cells, exploring DNA damage and repair mechanisms, analyzing cell cycle regulation, investigating apoptosis, exploring molecular virology, and evaluating vaccine and antibody-based cancer therapies. Molecular Cancer serves as an important platform for sharing exciting discoveries in cancer-related research. It offers an unparalleled opportunity to communicate information to both specialists and the general public. The online presence of Molecular Cancer enables immediate publication of accepted articles and facilitates the presentation of large datasets and supplementary information. This ensures that new research is efficiently and rapidly disseminated to the scientific community.