Chen Xinyi, Wang Kunyu, Liao Xingyu, Zheng Xingzheng, Yang Shuli, Han Chao, Lu Chang, Wang Xiaodan, Jin Lingge, Kang Haili, Han Yiding, Wei Jiacong, Fan Linyuan, Zhang Zhan, Kong Weimin
Department of Gynecology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, P. R. China.
Department of Gynecology Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China.
J Med Virol. 2025 Jan;97(1):e70183. doi: 10.1002/jmv.70183.
Small-cell neuroendocrine cancer (SCNEC) of the uterine cervix is an exceedingly rare, highly aggressive tumor with an extremely poor prognosis. The cellular heterogeneity, origin, and tumorigenesis trajectories of SCNEC of the cervix remain largely unclear. We performed single-cell RNA sequencing and whole-exome sequencing on tumor tissues and adjacent normal cervical tissues from two patients diagnosed with SCNEC of the cervix. Here, we provide the first comprehensive insights into the cellular composition, HPV infection-related features, and gene expression profiles of SCNEC of the cervix at single-cell resolution. Correlation analyses suggested that SCNEC of the cervix may originate from squamous epithelial cells, and this observation was validated with bulk RNA-seq data from external cervical neuroendocrine cancer. Furthermore, sex-determining region Y-box 2 (SOX2), a key transcription factor that functions in direct neural differentiation, was located in the copy number gain region and highly expressed in neuroendocrine tumor cells from both patients. Notable, the distributions of the HPV-infected epithelium and SOX2 highly expressed epithelium were consistent with each other. Therefore, we supposed that high-risk HPV infection and amplification of SOX2 in the squamous epithelium may contribute to the progression of small-cell neuroendocrine tumorigenesis in the cervix.
子宫颈小细胞神经内分泌癌（SCNEC）是一种极为罕见、侵袭性很强且预后极差的肿瘤。子宫颈SCNEC的细胞异质性、起源和肿瘤发生轨迹在很大程度上仍不清楚。我们对两名被诊断为子宫颈SCNEC的患者的肿瘤组织和相邻正常宫颈组织进行了单细胞RNA测序和全外显子测序。在此，我们首次在单细胞分辨率下对子宫颈SCNEC的细胞组成、HPV感染相关特征和基因表达谱提供了全面的见解。相关性分析表明，子宫颈SCNEC可能起源于鳞状上皮细胞，这一观察结果通过来自外部宫颈神经内分泌癌的批量RNA测序数据得到了验证。此外，性别决定区Y盒2（SOX2）是一种在直接神经分化中起作用的关键转录因子，位于拷贝数增加区域，并且在两名患者的神经内分泌肿瘤细胞中均高表达。值得注意的是，HPV感染的上皮和SOX2高表达的上皮分布相互一致。因此，我们推测鳞状上皮中高危HPV感染和SOX2扩增可能促成子宫颈小细胞神经内分泌肿瘤的发生发展。
