Xiang Xuesong, Tao Xiang, Hua Keqin, Jiang Hua, Ding Jingxin
Department of Gynecological Oncology, The Obstetrics and Gynecology Hospital of Fudan University, Shanghai, P. R. China.
Shanghai Key Laboratory of Female Reproductive Endocrine-related Diseases, The Obstetrics and Gynecology Hospital of Fudan University, Shanghai, P. R. China.
Commun Biol. 2025 Feb 5;8(1):184. doi: 10.1038/s42003-025-07605-y.
Small cell neuroendocrine cervical carcinoma (SCNECC) is an aggressive gynecological malignancy with poor prognosis. The precision therapeutic strategies for SCNECC are severely limited by the complex tumor microenvironment. Here, we mapped the single-cell landscape of a total of six samples from matched SCNECC cancerous foci and normal adjacent cervical tissues. Through analysis of 68,455 high-quality cells, malignant epithelial cells were identified with increased neuroendocrine differentiation and reduced keratinization. Within four epithelial cell clusters, the key transcription factors ASCL1, NEUROD1, POU2F3, and YAP1 defined molecular subtypes. Transitional trajectory among subtypes characterized two distinct carcinogenesis pathways in SCNECC. The P-type SCNECC showed potentially enhanced immune infiltration over other subtypes. Intercellular communication analysis identified several immune checkpoints and differentially expressed signaling pathways among subtypes. Through western blotting, the TC-YIK cell line was identified as an N-type SCNECC cell with high expression of SLFN11 and mTOR. Based on immunohistochemical staining of malignant subtyping markers, a cohort of 66 SCNECC patients from our hospital were divided into five subtypes. We further combined YAP1 expression with other clinicopathological factors (Cox p < 0.05) to establish a prognostic nomogram. Overall, these findings provide clues for tumorigenesis, precision treatments and prognostic prediction in SCNECC.
小细胞神经内分泌宫颈癌（SCNECC）是一种侵袭性妇科恶性肿瘤，预后较差。SCNECC的精准治疗策略受到复杂肿瘤微环境的严重限制。在此，我们绘制了来自匹配的SCNECC癌灶和正常相邻宫颈组织的总共六个样本的单细胞图谱。通过对68455个高质量细胞的分析，鉴定出恶性上皮细胞具有增加的神经内分泌分化和减少的角化。在四个上皮细胞簇中，关键转录因子ASCL1、NEUROD1、POU2F3和YAP1定义了分子亚型。亚型之间的过渡轨迹表征了SCNECC中两种不同的致癌途径。P型SCNECC显示出比其他亚型潜在增强的免疫浸润。细胞间通讯分析确定了几种免疫检查点以及亚型之间差异表达的信号通路。通过蛋白质印迹法，鉴定出TC-YIK细胞系为具有高表达SLFN11和mTOR的N型SCNECC细胞。基于恶性亚型标志物的免疫组织化学染色，将我院的66例SCNECC患者分为五个亚型。我们进一步将YAP1表达与其他临床病理因素相结合（Cox p < 0.05）以建立预后列线图。总体而言，这些发现为SCNECC的肿瘤发生、精准治疗和预后预测提供了线索。
