Disulfidptosis-Related Risk Model For Head And Neck Cancer

This study was designed to explore the HNSC-specific disulfidptosis-related risk model (HNSC-DRRM) and identify targets for the augmentation of immunotherapy in HNSC patients. Integrated algorithms strategy including consensus clustering, LASSO method and Cox regression were conducted in establishing the risk model. Single-cell transcriptome profiling and spacial-transcriptome analysis were performed to identified the key signaling in intercellular communication network. Patient-derived organotypic tumor spheroids (PDOTS) and murine MOC1 cell line-derived xenograft model were conducted for ex vivo and in vivo investigation for therapeutic target validation. The HNSC-DRRM demonstrated that patients with higher prognostic risk suffered a remarkably poorer survival probability compared with their counterparts (P < 0.001). The major pathways enriched in the low-risk group lay in adaptive immune response, antigen processing and presentation, and immune cells interactions, which were further supported by ORA and TIDE scores analysis. In addition, results from single-cell RNA-sequencing data described HNSC-DRRM as a multi-dimension model integrating both tumor cells and immune cell types, and indicated CXCL12-CXCR4 as key signaling in TME, which further supported by spatial transcriptomics analysis. Finally, we identified NQO1 as valuable theraputic target and found that dicoumarol could enhanced the anti-tumor effect of immune checkpoint therapy for HNSC. Overall, the present study manages to construct a risk model precisely related to disulfidptosis and provides novel combination treatment strategy for HNSC patients.