2. Academic Validation
  3. Single-cell and spatial dissection of precancerous lesions underlying the initiation process of oral squamous cell carcinoma

Single-cell and spatial dissection of precancerous lesions underlying the initiation process of oral squamous cell carcinoma

  • Cell Discov. 2023 Mar 13;9(1):28. doi: 10.1038/s41421-023-00532-4.
Lulu Sun # 1 2,  Xindan Kang # 1 2,  Chong Wang 1 2,  Rui Wang 1 2,  Guizhu Yang 1 2,  Wen Jiang 2 3,  Qi Wu 1 2,  Yujue Wang 1 2,  Yaping Wu 1 2,  Jiamin Gao 1 2,  Lan Chen 1 2,  Jie Zhang 1 2,  Zhen Tian 2 4,  Guopei Zhu 2 3,  Shuyang Sun 5 6
Affiliations

Affiliations

  • 1 Department of Oral and Maxillofacial-Head Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 2 College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China.
  • 3 Department of Oral and Maxillofacial-Head Neck Oncology, Division of Radiation Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 4 Department of Oral Pathology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 5 Department of Oral and Maxillofacial-Head Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. sunshuyang@sjtu.edu.cn.
  • 6 College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China. sunshuyang@sjtu.edu.cn.
  • # Contributed equally.
PMID: 36914617 DOI: 10.1038/s41421-023-00532-4
Abstract

Precancerous lesions of the oral mucosa, especially those accompanied by moderate to severe dysplasia, contribute to the initiation of oral squamous cell carcinoma (OSCC). However, the cellular compositions and spatial organization of the precancerous stage and how these factors promote human OSCC initiation remain unclear. Here, we built a single-cell transcriptome atlas and a spatial transcriptome map after obtaining data from pairwise human oral mucosal biopsies of 9 individuals consisting of very early-stage OSCC, adjacent precancerous lesions with moderate to severe dysplasia, as well as a matched normal region. An altered epithelial gene-expression profile was identified which favored OSCC initiation. This observation was coupled with distinct fibroblast, monocytic, and regulatory T-cell subclusters involved in reshaping the microenvironment. In particular, a unique immune-inhibitory monocyte subtype and spatial-switching regulation of VEGF signaling were observed surrounding precancerous lesions, concertedly strengthening activities in promoting Cancer initiation. Collectively, our work elucidated the cellular landscapes and roles of precancerous lesions underlying OSCC initiation, which is essential for understanding the entire OSCC initiation process and helps inform therapeutic strategies for Cancer intervention.

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