Supplementary file 1_Constructing Scissor+ risk model to predict prognosis and immunotherapy responses in PAAD by integrating bulk and single-cell RNA sequencing data.docx

BackgroundThis study focused on epithelial cells to construct a prognostic risk model and provide targeted insights into responses to immunotherapy.
MethodsSingle-cell RNA sequencing (scRNA-seq) was clustered using Uniform Manifold Approximation and Projection (UMAP) and a risk model was developed through Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. Kaplan-Meier analysis was performed to evaluate the prognosis of PAAD. The biological characteristics of LIPH were assessed using CCK-8, colony formation and Transwell assays.
ResultsEight major cell clusters were identified, revealing two developmental trajectories for malignant epithelial cells from primary to metastases. Epithelial cells were categorized into Scissor+ and Scissor- subtypes, with Scissor+ epithelial cells exhibiting more complex cellular communication with TME cells. Furthermore, we successfully developed a risk model for PAAD patients based on the Scissor findings. The prognosis for PAAD patients in the high-risk group was significantly poorer within both the TCGA and ICGC cohorts. Differences were observed in the populations of naïve B cells, CD8 T cells, M0 macrophages, and activated dendritic cells in different groups. Knockdown of LIPH significantly inhibited the growth and invasion of PAAD cells.
ConclusionThese findings underscore the significance of this risk model in predicting prognosis and immunotherapy responses, and enhancing understanding of tumor microenvironment (TME) heterogeneity in PAAD metastases.