Construction and multicohort validation of a colon cancer prognostic risk score system based on big data of neutrophil-associated differentially expressed genes.

ABSTRACT

Objective: To investigate the role of neutrophils in colon cancer progression. Methods: Genetic data from 1,273 patients with colon cancer were procured from public databases and categorized based on genes linked to neutrophils through an unsupervised clustering approach. Through univariate Cox regression analysis, differentially expressed genes (DEGs) influencing overall survival (OS) were identified, forming the basis for establishing a prognostic risk score (PRS) system specific to colon cancer. Additionally, the correlation between PRS and patient prognosis, immune cell infiltration, and intratumoral gene mutations were analyzed. Validation of PRS as an indicator for "pan-tumor" immunotherapy was conducted using four distinct immunotherapy cohorts. Results: The research identified two distinct subtypes of colon cancer, namely Cluster A and B, with patients in Cluster B demonstrating remarkably superior prognoses over those in Cluster A. A total of 17 genes affecting OS were screened based on 109 DEGs between the two cluster for constructing the PRS system. Notably, individuals classified under the high-PRS group (PRShigh) exhibited poorer prognoses, significantly linked with immune cell infiltration, an immunosuppressive tumor microenvironment, and increased genomic mutations. Remarkably, analysis of immunotherapy cohorts indicated that patients with PRShigh exhibited enhanced clinical responses, a higher rate of progression-free events, and improved overall survival post-immunotherapy. The PRS system, developed based on tumor typing utilizing neutrophil-associated genes, exhibited a strong correlation with prognostic elements in colon cancer and emerged as a vital predictor of "pan-tumor" immunotherapy efficacy. Conclusions: PRS serves as a prognostic model for patients with colon cancer and holds the potential to act as a "pan-tumor" universal marker for assessing immunotherapy efficacy across different tumor types. The study findings lay a foundation for novel antitumor strategies centered on neutrophil-focused approaches.