He Lewei, Wu Yuling, Lv Mingyi, Jiang Jiyang, Li Yifei, Guo Tao, Fan Zhenxin
Key Laboratory of Bioresources and Eco-Environment (Ministry of Education), College of Life Sciences, Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China.
Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.
Neuroendocrinology. 2025;115(1):13-33. doi: 10.1159/000542833. Epub 2024 Nov 27.
Small cell neuroendocrine carcinoma of the cervix (SCNECC) is a rare gynecologic malignant tumor, which has lack of systematic research. In order to investigate its molecular characteristics, origin, and pathogenesis, single-cell transcriptome sequencing (scRNA-Seq) of SCNECC was performed for the first time, the cellular and molecular landscape was revealed, and the key genes for clinical prognosis were screened.
This article initially performed the scRNA-Seq on a tumor tissue sample from an SCNECC patient, combined with scRNA-Seq data from a healthy cervical tissue sample downloaded from a public database; the single-cell transcriptome landscape was constructed. Then, we investigated the cell types, intratumoral heterogeneity, characteristics of tumor microenvironment, and potential predictive markers of SCNECC.
We identified two malignant cell populations, tumor stem cells and malignant carcinoma cells, and revealed two tumor progression pathways of SCNECC. By analyzing gene expression levels in the pathophysiology of SCNECC, we found that the expression levels of ERBB4 and NRG1, as well as the expression profile of mTOR signaling pathway mediated by them, were significantly upregulated in malignant carcinoma cells. In addition, we also found that carcinoma cells were able to stimulate malignant cell proliferation through the FN1 signaling pathway. The immune cells were in a stress state, with T-cell depletion, macrophage polarization, and mast cell glycolysis. These results suggested that carcinoma cells could interfere with immune response and promote tumor escape through MIF, TGFb, and other immunosuppressive-related signaling pathways.
This study revealed the mechanism of genesis and progression in SCNECC and the related important signaling pathways, such as mTOR, and provided new insights into the treatment of SCNECC.
宫颈小细胞神经内分泌癌（SCNECC）是一种罕见的妇科恶性肿瘤，目前缺乏系统研究。为了探究其分子特征、起源及发病机制，首次对SCNECC进行了单细胞转录组测序（scRNA-Seq），揭示了其细胞和分子层面的特征，并筛选出临床预后的关键基因。
本文首先对1例SCNECC患者的肿瘤组织样本进行scRNA-Seq，并结合从公共数据库下载的健康宫颈组织样本的scRNA-Seq数据，构建单细胞转录组图谱。然后，研究SCNECC的细胞类型、肿瘤内异质性、肿瘤微环境特征及潜在预测标志物。
我们鉴定出两个恶性细胞群体，即肿瘤干细胞和恶性癌细胞，揭示了SCNECC的两条肿瘤进展途径。通过分析SCNECC病理生理学中的基因表达水平，我们发现ERBB4和NRG1的表达水平以及由它们介导的mTOR信号通路的表达谱在恶性癌细胞中显著上调。此外，我们还发现癌细胞能够通过FN1信号通路刺激恶性细胞增殖。免疫细胞处于应激状态，表现为T细胞耗竭、巨噬细胞极化和肥大细胞糖酵解。这些结果表明，癌细胞可通过MIF、TGFb等免疫抑制相关信号通路干扰免疫反应并促进肿瘤逃逸。
本研究揭示了SCNECC的发生发展机制及相关重要信号通路，如mTOR，为SCNECC的治疗提供了新的见解。
