ITGA5 is a prognostic biomarker and correlated with immune infiltration in gastrointestinal tumors

Aman Xu,Haixing Zhu,Hai Zhu,Gang Wang

doi:10.1186/s12885-021-07996-1

Abstract

BackgroundIntegrin 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 tumors remain unclear.MethodsThe expression level of ITGA5 was 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, immunohistochemistry (IHC) staining and western blot 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.ResultsITGA5 was generally overexpressed and correlated with worse prognosis in multiple types of gastrointestinal tumors. In addition, ITGA5 expression level was significantly associated with tumor purity and immune infiltration levels of different immune cells in gastrointestinal 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 and western blot 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 was mainly involved in “integrin mediated signaling pathway”, “leukocyte migration”, “cell-substrate adhesion”.ConclutionsOur study demonstrated that ITGA5 may act as an essential regulator of tumor immune cell infiltration and a valuable prognostic biomarker in gastrointestinal tumors. Additional work is needed to fully elucidate the underlying mechanisms behind these observations.

Highlights

Integrin Subunit Alpha 5 (ITGA5), belongs to the integrin alpha chain family, is vital for promoting cancer cell invasion, metastasis
Hepatocellular carcinoma (LIHC) and gastric adenocarcinoma (STAD) were significantly higher compared with normal tissue levels (Fig. 1b)
Correlation between ITGA5 expression levels and patient prognosis To further identify the prognostic potential of ITGA5 in various cancers, clinical data from The Cancer Genome Atlas (TCGA) were used to explore the prognostic value of ITGA5 expression level using Gene Expression Profiling Interactive Analysis 2 (GEPIA2)

Summary

Introduction

Integrin Subunit Alpha 5 (ITGA5), belongs to the integrin alpha chain family, is vital for promoting cancer cell invasion, metastasis. The correlation between ITGA5 expression and immune infiltration in gastrointestinal tumors remain unclear. There is extensive evidence that tumor-infiltrating lymphocytes, such as tumor - associated macrophages (TAMs), influence both the prognosis and efficacy of chemotherapy and immunotherapy [5, 6], as well as tumor angiogenesis, progression and metastasis [7]. It is crucial to identify novel immune-related therapeutic targets and elucidate the potential mechanisms behind the immune interactions linked to gastrointestinal tumors. There is evidence revealing that immune components existing in the tumor microenvironment (TME) comprehensively regulate the biological behavior of the tumor through mutual interactions [17]. Immunotherapy, especially the application of immune checkpoint modulators, is an efficient treatment strategy for solid tumors [18, 19]

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Discussion

Conclusion