Fu Zi-Ming, Bao Yang-Yang, Dai Li-Bo, Zhong Jiang-Tao, Chen Heng-Chao, Chen Zhe, Zhou Shui-Hong
Department of Otolaryngology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Clin Cancer Res. 2025 Aug 1;31(15):3332-3343. doi: 10.1158/1078-0432.CCR-24-3679.
The mechanisms driving the progression of vocal cord leukoplakia (VCL) to laryngeal squamous cell carcinoma (LSCC) remain unclear, posing a significant barrier to the effective prevention, early diagnosis, and targeted treatment of LSCC. Therefore, it is essential to characterize the cellular microenvironmental differences between VCL and LSCC at single-cell resolution.
In the study, we conducted single-cell RNA sequencing and spatial transcriptomics on surgical tissue specimens obtained from 36 patients diagnosed with vocal cord polyps (VCP), VCL, and LSCC.
Our study generated the first single-cell atlas of VCP and VCL while expanding the cancer cell atlas of LSCC. This dataset comprises 318,907 cells and 12,679 spatial transcriptomic spots, allowing the identification of distinct cellular subclusters. We observed that VCL, as a transitional lesion between benign and malignant states, exhibits a hybrid microenvironment that mirrors VCP and LSCC, with early signs of immunosuppressive activity. Immunoregulatory cell populations demonstrate significant gene expression and functional pathway differences between VCL and LSCC.
Our single-cell RNA sequencing and spatial transcriptomics analyses revealed the cellular heterogeneity underlying benign, precancerous, and malignant laryngeal lesions. We identified epithelial subclusters in VCL with malignant potential and observed shared immunosuppressive features with LSCC, suggesting their role in disease progression. These findings provide valuable insights into the molecular transition from VCL to LSCC and emphasize potential targets for early diagnosis and therapeutic intervention.
声带白斑（VCL）进展为喉鳞状细胞癌（LSCC）的驱动机制仍不清楚，这对LSCC的有效预防、早期诊断和靶向治疗构成了重大障碍。因此，有必要在单细胞分辨率下表征VCL和LSCC之间的细胞微环境差异。
在本研究中，我们对36例诊断为声带息肉（VCP）、VCL和LSCC的患者的手术组织标本进行了单细胞RNA测序和空间转录组学分析。
我们的研究生成了首个VCP和VCL单细胞图谱，同时扩展了LSCC的癌细胞图谱。该数据集包含318,907个细胞和12,679个空间转录组学斑点，可识别不同的细胞亚群。我们观察到，VCL作为良性和恶性状态之间的过渡性病变，呈现出一种混合微环境，兼具VCP和LSCC的特征，并有免疫抑制活性的早期迹象。免疫调节细胞群体在VCL和LSCC之间表现出显著的基因表达和功能通路差异。
我们的单细胞RNA测序和空间转录组学分析揭示了良性、癌前和恶性喉部病变背后的细胞异质性。我们在VCL中鉴定出具有恶性潜能的上皮亚群，并观察到其与LSCC具有共同的免疫抑制特征，表明它们在疾病进展中的作用。这些发现为从VCL到LSCC的分子转变提供了有价值的见解，并强调了早期诊断和治疗干预的潜在靶点。
