Multi-omics Blueprint of Cellular Senescence in Deciphering Immune Characteristics and Prognosis Stratification of CRC

Abstract

Introduction: As one of the most common digestive system malignancies, colorectal cancer (CRC) imposed grave danger on the public health. Cellular senescence involves gradual changes in functionality and reproducibility leading to abnormalities, including apoptosis resistance and enhanced secretion of inflammatory factors. Methods Cellular senescence-related gene set was determined by the application of WCGNA. We performed single-cell annotations of CRC cells and determined crucial signaling pathways through Cell chat analysis. Using LASSO and Cox analyses, we identified a gene set with prognostic values. Our model was validated using independent external cohort. In addition, we employed ssGSEA and xCell analyses to describe the detailed profile of infiltrated immune cells. Results We identified 3 distinct cell clusters in CRC samples, including T cells, myeloid cells, and B cells. We found that MIF signaling to CD74 + CD44 and CXCR4 displayed the highest interaction probability in the B cells communication. We determined a set of 6 genes of prognostic significance, GPR88, PTH1R, SFRP2, GPX3, ELFN1, and MS4A2. The prognostic differences between the two groups in the internal and external sets were found to be statistically significant. We observed higher infiltration of the activated B cells, CD4 + T cells, and CD8 + T cells in the LR group, which was characterized with an inferior prognosis. The abundance of CD8 + T cells were highly correlated with plasmacytoid and activated dendritic cells and follicular T helper cells. Conclusion Our study developed a prognostic model based on cellular senescence, which demonstrated significant efficacy in stratifying patients with CRC. Our findings offer new insights into potential precision immune treatments for this disease, with the hope of improving patient outcomes.