ITGA5 Is a Prognostic Biomarker and Correlated with Immune Infiltration In Gastrointestinal Cancers

Abstract

Background: Integrin Subunit Alpha 5 (ITGA5) belongs to the integrin alpha chain family, is vital for promoting cancer cell invasion, metastasis. However, the correlation between ITGA5 expression and immune infiltration in gastrointestinal (GI) tumors remain unclear.Methods: The expression levels of ITGA5 were detected by Oncomine and Tumor Immune Estimation Resource (TIMER). The association between ITGA5 and prognosis of patients was identified by Kaplan–Meier plotter, Gene Expression Profiling Interactive Analysis 2(GEPIA2) and PrognoScan. We evaluated the correlation between ITGA5 expression and immune infiltrating level via TIMER. Besides, TIMER and immunohistochemistry (IHC) staining were used to explore correlations between ITGA5 expression and markers of immune infiltrates cells. Furthermore, we constructed protein-protein interaction (PPI) network and performed functional enrichment by GeneMANIA and Metascape.Results: ITGA5 was generally overexpressed and correlated with worse prognosis in multiple types of GI tumors. In addition, ITGA5 expression levels was significantly associated with tumor purity and immune infiltration levels of different immune cells in GI tumors. Interestingly, Immune markers for monocytes, tumor - associated macrophages (TAMs), macrophages 2 (M2) cells and T-helper 2 (Th2) cells were found to be significantly and positively correlated with ITGA5 expression levels in colon and gastric cancer. Results from IHC staining further proved that markers of Th2 and M2 cell were significantly increased in gastric cancer patients with high ITGA5 expression levels. Lastly, interaction network and function enrichment analysis revealed ITGA5 were mainly involved in “integrin mediated signaling pathway”, “leukocyte migration”, “cell-substrate adhesion”.Conclutions: our study demonstrated that ITGA5 may act as an essential regulator of tumor immune cell infiltration and a valuable prognostic biomarker in GI tumors. Additional work is needed to fully elucidate the underlying mechanisms behind these observations.