State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Oral Dis. 2024 Mar;30(2):172-186. doi: 10.1111/odi.14347. Epub 2022 Sep 8.
Proliferative verrucous leukoplakia (PVL) is characterized by a spectrum of clinicopathological features and a high risk of malignant transformation. In this study, we aimed to delineate the dynamic changes in molecular signature during PVL progression and identify the potential cell subtypes that play a key role in the premalignant evolution of PVL.
We performed single-cell RNA sequencing on three biopsy samples from a large PVL lesion. These samples exhibited a histopathological continuum of PVL progression.
By analyzing the transcriptome profiles of 27,611 cells from these samples, we identified ten major cell lineages and revealed that cellular remodeling occurred during the progression of PVL lesions, including epithelial, stromal, and immune cells. Epithelial cells are shifted to tumorigenic states and secretory patterns at the premalignant stage. Immune cells showed growing immunosuppressive phenotypes during PVL progression. Remarkably, two novel cell subtypes INSR endothelial cells and ASPN fibroblasts, were discovered and may play vital roles in microenvironment remodeling, such as angiogenesis and stromal fibrosis, which are closely involved in malignant transformation.
Our work is the first to depict the cellular landscape of PVL and speculate that disease progression may be driven by functional remodeling of multiple cell subtypes.
增殖性疣状白斑（PVL）的特征是一系列临床病理特征和恶性转化的高风险。本研究旨在描绘 PVL 进展过程中分子特征的动态变化，并确定在 PVL 癌前演变中起关键作用的潜在细胞亚型。
我们对来自一个大的 PVL 病变的三个活检样本进行了单细胞 RNA 测序。这些样本表现出 PVL 进展的组织病理学连续体。
通过分析来自这些样本的 27611 个细胞的转录组谱，我们鉴定出了十个主要的细胞谱系，并揭示了在 PVL 病变进展过程中发生的细胞重塑，包括上皮细胞、基质细胞和免疫细胞。上皮细胞在癌前阶段向肿瘤发生状态和分泌模式转变。值得注意的是，发现了两种新的细胞亚型 INSR 内皮细胞和 ASPN 成纤维细胞，它们可能在微环境重塑中发挥重要作用，如血管生成和基质纤维化，这些过程与恶性转化密切相关。
我们的工作首次描绘了 PVL 的细胞景观，并推测疾病进展可能是由多种细胞亚型的功能重塑驱动的。
