PANoptosis-driven molecular stratification in esophageal squamous cell carcinoma: A multi-omics prognostic model and FGFR-Targeted therapeutic validation

作者：Zhiqiang Yi, Ting Tao, Qiqi Zhang, Xiaojia Liu, Cancan Wang, Hui Li, Xiujuan Li, Zhiqiang Zhang · 发表于：Computers in Biology and Medicine · 年份：2025 · DOI：10.1016/j.compbiomed.2025.110688 · 被引用次数：2 · 研究领域：Ferroptosis and cancer prognosis、Inflammasome and immune disorders、Inflammatory Biomarkers in Disease Prognosis

BACKGROUND: Esophageal squamous cell carcinoma (ESCC), accounting for approximately 90 % of esophageal cancer (EC) cases globally, is characterized by aggressive metastasis and poor prognosis. PANoptosis, an integrated form of pyroptosis, apoptosis, and necroptosis, has emerged as a potential predictor of cancer survival and therapy response. However, its role in ESCC remains unclear. METHODS: Using univariate and LASSO Cox regression analyses, we identified prognostic PANoptosis-related genes (PRGs) to construct a risk model that stratified patients into high- and low-risk groups. The model's accuracy was validated using Kaplan-Meier analysis, receiver operating characteristic (ROC) curves, and nomograms. Differential pathways were investigated using gene set enrichment analysis (GSEA), while the significance of genes was highlighted through single-cell RNA sequencing (scRNA-seq) analysis. In vitro experiments validated the tumor-suppressive effects of AZD4547, an FGFR inhibitor. This study elucidates the PANoptosis-driven mechanisms underlying the prognosis and therapeutic strategies for ESCC. RESULTS: Thirteen PRGs (CCNE1, CEACAM1, CR2, CRYAB, ERBB3, GAST, HELLS, IFT57, KLF5, MAPK13, PLAU, SAP18, SPATA4) associated with survival were identified and formed the foundation of a robust prognostic model. The model was validated in one external microarray cohort and an independent RNA-seq cohort. Immune microenvironment analysis revealed distinct differences in immune infiltrati...