Elucidating the Characteristics and Functional Significance of Disulfidptosis-related Genes in Head and Neck Squamous Cell Carcinoma

Abstract Disulfidptosis is a newfound programmed cell death (PCD) mode characterized by disulfide stress. Several computer-aided bioinformatic analyses were performed to elucidate the characteristics and functional significance of disulfidptosis-related genes in head and neck squamous cell carcinoma (HNSCC). The relative compositions of cells in the tumor microenvironment (TME), mutant landscape, lasso regression analysis, and predicted clinical outcome were performed by analyzing bulk RNA-sequence data. The prognostic model was verified by qRT-PCR. Besides, single-cell sequence data (scRNA) was analyzed by Seurat, CopyKAT, and monocle2 to reveal the expression characteristics of disulfidptosis-related genes. Moreover, the spatial distribution characteristics of each cell subgroup in the section and the functional significance of cancer-associated fibroblasts (CAFs) were clarified by STUtility, SpaCET, and SPATA2. Here, two clusters with different expression characteristics of disulfidptosis-related genes were identified. Cluster 1 (C1) patients had a worse prognosis and a higher proportion of stromal cells but lower effector T cell infiltration than cluster 2 (C2). A novel prognostic model was established and verified in our patient cohort. Additionally, diploid and inflammatory CAFs showed higher disulfidptosis-related gene expression levels. Furthermore, disulfidptosis-related genes exhibited extensive and differential spatial expression on tissue sections. Collectively, our study may contribute to revealing the function of disulfidptosis, and improve the expansion of knowledge of crosstalk between cancer cells and CAFs.