Prognostic implication of ITGB8 and its relationship with immune response

Abstract

Abstract Background Integrin β8 (ITGβ8) belongs to the β subunit family of integrin. It plays a role in cells and extracellular matrix participating in the proliferation and metastasis of tumours. It is upregulated in various cancers, including non-small-cell lung cancer (NSCLC). Researches show that ITGβ8 may be involved in regulating immunity escape in some tumors. However, it is still unclear whether ITGβ8 is involved in the immune regulation of NSCLC. Here, bioinformatics analysis and basic experiments were used to investigated the expression of ITGβ8 and its potential association with immune in NSCLC. Methods We used bioinformatics technology to analyze not only the expression of ITGβ8 in NSCLC tissues in database, but also the correlation between ITGβ8 expression and immune cell infiltration, TMB, immune checkpoint genes, signaling pathways and patient survival. The expression of ITGβ8 in NSCLC cells was verified by WB and RT-qPCR. Kaplan-Meier survival curves were used to analyze the relationship between ITGβ8 expression and prognosis. Log-rank test and Cox proportional-hazards model were used to identify risk factors. Results The TCGA and HPA database as well as our NSCLC tissue specimens showed high expression of ITGβ8 in NSCLC. Its expression was positively correlated with lymph node metastasis and TNM stage. ITGβ8 expression was downregulated in type C3 (inflammatory) and upregulated in C6 (TGF-β dominant) immune subtypes in LUAD and LUSC. In LUAD, the expression of ITGβ8 was significantly positively correlated with macrophages and NK cells. It is negative related to CD8 T cells and Th17 cells in both LUAD and LUSC. KEGG analysis revealed that ITGβ8 was significantly involved in activation of MAPK signaling pathway, TNF signaling pathway and Hippo signaling pathways, et. Highly expressed ITGβ8 has a shorter survival in NSCLC. Patients with high ITGβ8 expression were significantly shorter survival compared with low ITGβ8 expression who receiving immunotherapy. The objective response rate was 66.7% for high ITGβ8 expression compared with 52.4% for low ITGβ8 expression. Conclusions ITGβ8 is highly expressed in NSCLC and is involved in regulating the immune process of NSCLC. It may be an important immune predictive biomarker that provides a new idea for the treatment of NSCLC.