Identification of microsatellite instability and immune-related prognostic biomarkers in colon adenocarcinoma

Abstract

Background: Colon adenocarcinoma (COAD) is a prevalent malignancy that causes significant mortality. Microsatellite instability plays a pivotal function in COAD development and immunotherapy resistance. However, the detailed underlying mechanism requires further investigation. Consequently, identifying molecular biomarkers with prognostic significance and revealing the role of MSI in COAD is important for addressing key obstacles in the available treatments.

Methods: CIBERSORT and ESTIMATE analyses were performed to evaluate immune infiltration in COAD samples, followed by correlation analysis for MSI and immune infiltration. Then, differentially expressed genes (DEGs) in MSI and microsatellite stability (MSS) samples were identified and subjected to weighted gene co-expression network analysis (WGCNA). A prognostic model was established with univariate cox regression and LASSO analyses, then evaluated with Kaplan-Meier analysis. The correlation between the prognostic model and immune checkpoint inhibitor (ICI) response was also analyzed.

Results: In total, 701 significant DEGs related to MSI status were identified, and WGCNA revealed two modules associated with the immune score. Then, a seven-gene prognostic model was constructed using LASSO and univariate cox regression analyses to predict survival and ICI response. The high-risk score patients in TCGA and GEO cohorts presented a poor prognosis, as well as a high immune checkpoint expression, so they are more likely to benefit from ICI treatment.

Conclusion: The seven-gene prognostic model constructed could predict the survival of COAD and ICI response and serve as a reference for immunotherapy decisions.

Keywords: colon adenocarcinoma (COAD); drug response; immune microenvironment; microsatellite instability (MSI); prognostic biomarkers.