Chen Wanling, Wang Yang, Yao Zhengduo, Gu Ting, Hu Yuhua, Leng Nannan, Zhang Chunye, Tian Zhen, Li Jiang
Department of Oral Pathology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai, China.
NPJ Precis Oncol. 2025 Jun 17;9(1):189. doi: 10.1038/s41698-025-00974-x.
Salivary carcinoma ex pleomorphic adenoma (CXPA) is a carcinoma that develops from benign pleomorphic adenoma, and it is characterized by aggressiveness and poor prognosis. Recent advancements in cancer stem cell (CSC) research have identified CSCs as critical contributors to tumor carcinogenesis due to their unlimited self-renewal ability. Single-cell RNA sequencing has enabled a comprehensive analysis of CSC heterogeneity. However, CSCs in CXPA remain largely unexplored. In this study, we constructed a comprehensive atlas of CXPA at single-cell resolution and demonstrated that CXPA exhibited intratumoral heterogeneity. We identified four tumor epithelial cell subgroups characterized by epithelial development, cell cycle, extracellular matrix remodeling, and salivary secretion signatures. ECT2 tumor cells in the cell cycle cluster were identified as CSCs in CXPA. Analysis of tumor tissues from patients with CXPA revealed that ECT2 expression was strongly associated with invasiveness and prognosis. Targeting the ECT2 gene significantly inhibited tumor sphere formation and aggressiveness in CXPA cell lines. Our findings provide new insights into CXPA diversity and origin, with substantial clinical implications for targeting the ECT2 gene in CXPA treatment.
涎腺多形性腺瘤恶变（CXPA）是一种由良性多形性腺瘤发展而来的癌，其特点是具有侵袭性且预后较差。癌症干细胞（CSC）研究的最新进展已将CSC确定为肿瘤发生的关键因素，因为它们具有无限的自我更新能力。单细胞RNA测序能够对CSC的异质性进行全面分析。然而，CXPA中的CSC在很大程度上仍未被探索。在本研究中，我们构建了单细胞分辨率的CXPA综合图谱，并证明CXPA表现出肿瘤内异质性。我们鉴定出四个肿瘤上皮细胞亚群，其特征分别为上皮发育、细胞周期、细胞外基质重塑和唾液分泌特征。细胞周期簇中的ECT2肿瘤细胞被鉴定为CXPA中的CSC。对CXPA患者肿瘤组织的分析表明，ECT2表达与侵袭性和预后密切相关。靶向ECT2基因可显著抑制CXPA细胞系中的肿瘤球形成和侵袭性。我们的研究结果为CXPA的多样性和起源提供了新的见解，对CXPA治疗中靶向ECT2基因具有重要的临床意义。
