A Pan-Cancer Analysis of the Oncogenic Role of Integrin Beta4 (ITGB4) in Human Tumors

Abstract

Background Integrin beta4 (ITGB4) is a transmembrane receptor that plays a key role in tumorigenesis and tumor development. However, there are no pan-cancer analyses of ITGB4. Methods This study demonstrates the first potential oncogenic roles of ITGB4 across 33 tumors based on the dataset of the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Results ITGB4 is highly expressed in many cancers, and distinct correlations exist between ITGB4 expression and the prognosis of tumor patients. We also found that the methylation and genetic alteration level of ITGB4 was associated with some cancer prognosis. Furthermore, we found a reduced phosphorylation of ITGB4 at S1457 in several tumors, such as breast and ovarian cancers. Finally, ITGB4 expression was correlated with cancer-associated fibroblasts in liver hepatocellular carcinoma and prostate adenocarcinoma, and the infiltration level of NK cells and neutrophils was observed in other cancers, such as breast invasive carcinoma and lung adenocarcinoma. Moreover, RNA metabolism and protein processing-associated functions are involved in the functional mechanism of ITGB4. Conclusion Our first pan-cancer study may offer a relatively comprehensive understanding of the oncogenic roles of ITGB4 across different tumors.

Identification and Validation of Anoikis-Related Signatures for Predicting Prognosis in Lung Adenocarcinoma with Machine Learning

“… 30 Moreover, bioinformatics analysis showed that ITGB4 acts as a pan-cancer oncogene in 33 different types of human tumors. 31 ITGB4 overexpression has been associated with venous invasion and decreased overall survival in patients with NSCLC. 32 ITGB4 has also been closely associated with other respiratory diseases, including spontaneous inflammation of the lungs, airway inflammation and hyperreactivity, and acute lung injury.…”

Exosomal cargos-mediated metabolic reprogramming in tumor microenvironment

“…The exosomal miR-105 secreted by breast cancer (BC) targets MXI1, activates the MYC pathway in CAFs, enhances the glycolysis and glutamine decomposition of CAFs, and detoxifies the metabolites (lactate and NH4 +) to fuel adjacent cancer cells [238]. ITGB4 is highly expressed in various cancers and contributes to tumor progression [272]. Studies on triple-negative breast cancer (TNBC) found that cancer cell-derived exosomal ITGB4 could be delivered to CAFs to induce BNIP3L-dependent mitophagy and lactate production in CAFs.…”

Therapeutic Implications of the Drug Resistance Conferred by Extracellular Vesicles Derived from Triple-Negative Breast Cancer Cells

“…Transmembrane proteins on the surface of TNBC-EVs also contribute to the metabolic reprogramming of CAFs. Upregulation of integrin β (ITGB4) is associated with tumor progression [ 124 ]. Interestingly, ITGB4 is not expressed in CAFs, but its expression is induced by contact with TNBC cells [ 125 ].…”