The Tumor-Associated Neutrophils-Related Signatures Predict Prognosis and Indicate Immune Landscape in Colorectal Carcinoma.

Abstract

Background: Tumor-associated neutrophils (TANs), a major immune cell type in the tumor microenvironment (TME), are associated with antitumor or pro-tumor phenotypes. A wealth of evidence evidences demonstrated that the content of TANs has been implicated in the pathogenesis of cancer and may be ideal targets for cancer therapy. In this study, we identified TANs-related genes to construct a prognostic model and evaluated its potential as a biomarker for predicting prognosis and immunotherapeutic response in colorectal carcinoma (CRC). Methods: Kaplan-Meier survival curves were used to assess the impact of TANs infiltration on patient survival. Weighted Gene Co-Expression Network Analysis (WGCNA) identified genes associated with TANs. Univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression were applied to filter TANs-related risk signatures. A prognostic model was constructed using data from The Cancer Genome Atlas (TCGA) and validated with the GSE39582 dataset. Immune cell infiltration levels and immunotherapy responses were compared between high- and low-risk groups. Functional enrichment analysis was performed to identify relevant Gene Ontology (GO) terms and pathways. Results: Patients with elevated TANs levels have a low survival rate. Fourteen risk signature genes were identified, and a risk model was constructed based on these genes. Patients in the high-risk group had worse survival outcomes and improved responsiveness to immunotherapy. Conclusions: This study comprehensively analyzed the role of TANs in CRC progression and developed a prognostic model based on TANs-related genes, which holds significant potential for predicting prognosis and immunotherapy outcomes in CRC patients.