The bioinformatics and experimental analysis of CD276 for prognosis and immune infiltrates in colon adenocarcinoma

Abstract

BackgroundColon adenocarcinoma (COAD), although the third-most common type of gastrointestinal tumors, still lacks specific biomarkers for early diagnosis, treatment, and prognosis. CD276, an immune checkpoint, is upregulated in various cancers.This study aimed to evaluate the role of CD276 in tumorigenesis, prognosis and immunity for COAD.MethodsThe expression profile of CD276 gene in COAD was established by using RNA-sequencing transcriptomic data of The Cancer Genome Atlas (TCGA) databases. The biological functions of CD276 were evaluated using the Metascape database and Gene Set Enrichment Analysis (GSEA). The association between CD276 and immune cell infiltration was investigated by TIMER website. Correlation analysis was performed between CD276 expression and clinicopathological characteristics. Cox proportional hazard regression and Kaplan-Meier final analysis were applied for identifying the prognostic role of CD276. ResultsCD276 expression was significantly elevated in COAD tumor (P < 0.0001). Functional annotation revealed many enriched GO-terms among which the activity of the growth factor, cell adhesion and corresponding cancer-related pathways were highly represented in high CD276 expression phenotype. High CD276 was associated with microsatellite instability (MSI) status, patients’ survival, and disease progression. Cox regression analysis revealed that CD276 was a risk factor for overall survival [hazard ratio (HR): 1.848, P = 2.64E−03], disease-specific survival (HR: 2.406, P = 5.35E−04), and progression-free interval (HR: 1.772, P = 2.04E−03). Moreover, CD276 level was significantly associated with tumor immune cell infiltration, biomarkers of immune cells, and immune checkpoint expression.ConclusionsOur analyses indicated that increased CD276 may contribute to COAD development by activing tumor‐promoting signal pathways and altering the immune microenvironment. It is believed that abnormal expression of CD276 has clinical prognostic value in COAD patients.