<scp>ITGB1</scp> as a prognostic biomarker correlated with immune suppression in gastric cancer

Abstract

INTRODUCTION: Gastric cancer is one of the common malignant tumors with a high incidence and mortality in China. Prognostic biomarkers and potential predictors of the treatment efficacy of gastric cancer urgently need to be identified. Integrin-β (ITGB) is a superfamily of integrins and is involved in cell adhesion, tissue repair, immune response, and tumor metastasis. METHODS: We analyzed ITGB1 expression in our hospital samples of the gastric cancer cohort. And the public data of The Cancer Genome Atlas stomach adenocarcinoma (TCGA-STAD), The Asian Cancer Research Group (ACRG)/GSE62254, and GSE15459 data sets were analyzed by using the bioinformatic methods. The relationships between ITGB1 expression and clinicopathological features, patient prognosis, activation of the Wnt/β-catenin signaling pathway, and tumor immunosuppressive factors were also explored. RESULTS: The positive rate of ITGB1 expression in the Fudan University Shanghai Cancer Center gastric cancer tumor tissues was 61.4% (258/420) and correlated with deep invasion (p = 0.017), an advanced clinical stage (p = 0.011), and a poor prognosis (p < 0.05). The TCGA-STAD/ACRG/GSE15459 cohorts also showed similar results. ITGB1 is one of the upstream molecules of the Wnt/β-catenin signaling pathway and is correlated with tumor immune suppression. In gastric cancer, we found a correlation between ITGB1 expression and Wnt/β-catenin signaling pathway activity. In the TCGA-STAD/ACRG/GSE15459 cohorts, ITGB1 expression was positively associated with immunosuppressive factors and negatively associated with immunoactive factors. Patients with low ITGB1 expression exhibited a significantly high immunotherapy response ratio according to an analysis of tumor immune dysfunction and exclusion (TIDE), which may indicate that ITGB1 is a potential predictor of immunotherapy efficacy. CONCLUSIONS: ITGB1 affects the prognosis in gastric cancer patients and plays a core role in immune suppression in gastric cancer.