Colorectal cancer subtyping and prognostic model construction based on interleukin-related genes

Abstract

Background: Members of the interleukin (IL) family are closely linked to cancer development and progression. But research on prognosis of colorectal cancer (CRC) related to IL is still lacking. This study investigated new CRC prognostic markers and offered new insights for CRC prognosis and treatment.Methods: CRC-related data and IL gene data were collected from public databases. Sample clustering was done with NMF package to divide samples into different subtypes. Differential, enrichment, survival, and immune analyses were conducted on subtypes. A prognostic model was constructed using regression analysis. Drug sensitivity analysis was performed using GDSC database. Western blot was performed to assess effect of IL7 on the JAK/STAT signaling pathway. Flow cytometry was utilized to examine impact of IL7 on CD8+ T cell apoptosis.Results: Two CRC subtypes based on IL-associated genes were obtained. Cluster1 had a higher survival rate than Cluster2, and they showed differences in some immune levels. The two clusters were mainly enriched in the JAK-STAT signaling pathway, Th17 cell differentiation, and IL-17 signaling pathway. An 11-gene signature was built, and Riskscore was an independent prognosticator for CRC. Low-risk group showed higher sensitivity to nine common targeted anticancer drugs. Western blot and flow cytometry results demonstrated that IL7 could phosphorylate STAT5 and promote survival of CD8+ T cells.Conclusion: This study divided CRC samples into two IL-associated subtypes and obtained an 11-gene signature. Additionally, targeted drugs that may improve prognosis of CRC patients were identified. These findings are of paramount importance for patient's prognosis and CRC treatment.