A multi-cancer analysis unveils ITGBL1 as a cancer prognostic molecule and a novel immunotherapy target

Abstract

Objectives Integrin subunit beta-like 1 (ITGBL1), a member of the epidermal growth factor (EGF)-like protein family, encodes a beta integrin-related protein that is mainly associated with the development of specific tumours and immune-related signalling pathways. This work aimed to explore the possibility that ITGBL1 functions as a novel target gene for immunotherapy and could be a cancer prognostic molecule. Methods The mRNA data for ITGBL1 were obtained from the public databases The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) and Gene Expression Omnibus (GEO). Using GEPIA, the differential expression of ITGBL1 in different tumour stages was identified. Cancer prognostic correlations were explored using Kaplan–Meier survival analysis and forest plots. A combination of Gene Set Enrichment Analysis (GSEA), TIMER2.0 and the R package was applied to analyse the ITGBL1-enriched related pathways. The NCI-60 drug database was examined using CellMinerTM. Cytological experiments were conducted to confirm ITGBL1’s impact on cancer cells. Results Our research has shown that ITGBL1 is differentially expressed in 26 cancers, and high ITGBL1 expression predicts a poorer survival prognosis in some specific cancers. Additionally, we found that ITGBL1 is enriched in immune-related pathways, which are closely linked to immunomodulatory molecules, immune-infiltrating cells, and immunomodulatory factors. The results of tumor mutational burden (TMB) and microsatellite instability (MSI) also indicate that the expression of ITGBL1 is beneficial for improving tumor immunotherapy efficacy. Furthermore, a number of antitumor agents associated with ITGBL1 expression have been identified. Finally, knockdown of ITGBL1 restricts the ability of gastric and colorectal cancer cells to proliferate and migrate. Conclusions Our study demonstrates that ITGBL1 can be utilized to accurately prognosticate cancer and has opened up new avenues for the investigation of tumor immune mechanisms and the development of more efficacious immunotherapies.