Multi-omics analysis deciphers intercellular communication regulating oxidative stress to promote oral squamous cell carcinoma progression

Oral squamous cell carcinoma (OSCC) is a common malignant tumor in the head and neck, associated with high recurrence and poor prognosis. We performed an integrated analysis of single-cell RNA and spatial transcriptomic data from cancerous and normal tissues to create a comprehensive atlas of epithelial cells and cancer-associated fibroblasts (CAFs). Our findings show that AKR1C3⁺ epithelial cells, located at the tumor's stromal front, exhibit significant copy number variation and poor prognostic indicators, suggesting a role in tumor invasion. We also identified a distinct group of early-stage CAFs (named OSCC_Normal, characterized by ADH1B⁺, MFAP4⁺, and PLA2G2A⁺) that interact with AKR1C3+ cells, where OSCC_Normal may inhibit the FOXO1 redox switch in these epithelial cells via the IGF1/IGF1R pathway, causing oxidative stress overload. Conversely, AKR1C3⁺ cells use ITGA6/ITGB4 receptor to counteract the effects of OSCC_Normal, promoting cancer invasion. This study unveils complex interactions within the OSCC tumor microenvironment.