ITGB5 is a prognostic factor in colorectal cancer and promotes cancer progression and metastasis through the Wnt signaling pathway

Integrin beta5 (ITGB5) expression levels are dysregulated in a variety of cancers. However, the mechanism and clinical value of ITGB5 in colorectal cancer (CRC) remain unclear. The Gene Expression Omnibus (GEO) database, real-time PCR, Western blotting and immunohistochemistry were utilized to evaluate ITGB5 expression levels in CRC tissue. Clinical data from the GEO database were obtained to further explore the associations of ITGB5 with clinical features and patient survival. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and gene set enrichment analysis (GSEA) were performed to explore the functions and signaling pathways of ITGB5. In addition, ITGB5 expression was inhibited by siRNA, and the roles of ITGB5 in SW480 and RKO cell growth, migration and invasion, as well as in the Wnt/β-catenin signaling pathway, were investigated. Pancancer studies have shown that ITGB5 is highly expressed in a variety of cancers. Moreover, ITGB5 expression is significantly increased in CRC tissues and is correlated with TNM stage, invasion depth, lymph node metastasis and distant metastasis stage. Kaplan-Meier analysis and meta-analysis of the GSE39582 and GSE17538 datasets indicated that a high level of ITGB5 is a high risk factor for overall survival (OS) and disease-free survival (DFS). In addition, receiver operating characteristic (ROC) curve analysis revealed the value of ITGB5 in predicting DFS, and univariate and multivariate analyses showed that ITGB5 may be an independent prognostic factor for DFS. GO and KEGG analyses indicated that many GO terms related to the extracellular matrix (ECM), focal adhesion and ECM-receptor interaction pathways were enriched. GSEA revealed focal adhesion, cancer pathways, ECM-receptor interactions and Wnt signaling pathways in the samples with high ITGB5 expression. Correlation analysis revealed that high ITGB5 expression is significantly correlated with the TGF-β/EMT pathway and WNT targets. Silencing of ITGB5 inhibited SW480 and RKO cell proliferation, invasion and migration. Mechanistically, downregulated ITGB5 expression blocked the Wnt/β-catenin signaling pathway and epithelial-mesenchymal transition (EMT) in CRC cells. Moreover, ITGB5 expression was related to M0 macrophages, M2 macrophages, neutrophils and plasma cell fractions. ITGB5 may be associated with poor prognosis and metastasis in patients with CRC. ITGB5 may hold promise as a prognostic biomarker and a new potential therapeutic target for CRC.