US7

[US7-06] Mechanism on oral caricnogenesis and oral cancer development

〇Yasusei Kudo¹ (1. Dept Oral Biosci, Tokushima Univ Grad Sch Inst Biomed Sci)

Keywords:口腔がん、遺伝子変異、部分的上皮間葉転換

Head and neck squamous cell carcinoma (HNSCC) is a globally prevalent cancer with a rising incidence rate. While chemotherapy, radiation therapy, and targeted drugs such as cetuximab and nivolumab have been approved for treatment, the 5-year survival rate for HPV-negative HNSCC has not improved significantly. Genetic mutation analysis in HNSCC cases has consistently shown frequent mutations in TP53, FAT1, and CDKN2A genes in HPV-negative cases. To elucidate their involvement, we generated knock-in mice with these commonly observed genetic mutations, aiming to simulate the development of oral cancer. Among them, Fat1 knock-in mice exhibited embryonic lethal, revealing mandibular and tongue defects associated with morphological abnormalities in the first pharyngeal arch. Furthermore, we conducted subset classification of HNSCC cases to enhance our understanding of the disease. The reanalysis of publicly available single-cell RNA sequencing data resulted in the classification of HNSCC into three subsets. One of these subsets demonstrated a strong correlation with partial epithelial-mesenchymal transition (partial-EMT), which is known to be associated with aggressive behavior and lymph node metastasis in HNSCC. Additionally, we identified a multitude of previously unreported partial-EMT-related genes through marker gene calculations for each subset. Clustering using these marker genes allowed for similar classification of TCGA cohorts and HNSCC cell lines. Currently, our research is focused on characterizing the properties of each subset and conducting functional analysis of the identified partial-EMT-related genes. In this presentation, we aim to share the latest insights from our ongoing research on oral cancer.