Identification of differentiation markers and immune microenvironment in head and neck squamous cell carcinoma using machine learning combined with single-cell analysis

Our findings highlight significant molecular differences between well-differentiated and poorly differentiated HNSCC, with low CRABP2 expression identified as a critical driver of poorly differentiated HNSCC and a central factor in the immune-suppressive tumor microenvironment. For the first time, we report that poorly differentiated HNSCC are associated with an immune-suppressive microenvironment, characterized by increased Treg infiltration and decreased neutrophil infiltration, which may contribute to their worse prognosis. This study identifies novel marker genes associated with HNSCC differentiation and offers new insights into the mechanisms driving tumor differentiation. These results pave the way for developing personalized therapeutic strategies targeting differentiation pathways and immune modulation, aiming to improve treatment outcomes for HNSCC patients.