PANoptosis in deciphering immune characteristics and prognosis stratification of CRC

Colorectal cancer (CRC), the third most prevalent cancer type, poses a significant public health threat due to its high metastasis rate and deep bowel wall invasion. PANoptosis is a newly discovered proinflammatory programmed cell death. In this study, we annotated CRC cells at single-cell resolution, conducted Cell chat and PROGENy analyses to determine key carcinogenic and signaling pathways, and used LASSO and Cox analyses to identify a prognostic gene set, validated in two independent external cohorts. ssGSEA and xCell analyses characterized the infiltrated immune cell profile. We identified four distinct cell clusters (CD8 + T cells, CD4 + T cells, myeloid cells, B cells), found CD8 + T cells as primary signal transducers via CLEC and MIF pathways, and constructed a PANoptosis-based prognostic model using eight hub genes (CCL20, CPVL, GRN, IMP3, LGALS2, MS4A1, PLEKHF4, TIMP1). The model showed accuracy and stability in external cohorts. The high-risk group exhibited higher infiltration of type 1 T helper cells, T follicular helper cells, natural killer cells, natural killer T cells, dendritic cells, activated CD8 + T cells, myeloid-derived suppressor cells, and regulatory T cells, associated with poorer outcomes. This PANoptosis-based model effectively stratifies CRC patients, offering new insights for precise immune therapy.