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

BMC Cancer

Haixing Zhu¹  Hai Zhu²  Aman Xu³  Gang Wang⁴ 

[1] Department of Gastrointestinal Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, 230031, Hefei, People’s Republic of China;Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, 230001, Hefei, People’s Republic of China;Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, 230001, Hefei, People’s Republic of China;Department of General Surgery, The Fourth Affiliated Hospital of Anhui Medical University, 230001, Hefei, People’s Republic of China;Department of General Surgery, The Fourth Affiliated Hospital of Anhui Medical University, 230001, Hefei, People’s Republic of China;

关键词: ITGA5;    Gastrointestinal tumor;    Immune;    Prognosis;    Tumor-associated macrophages;   

DOI  :  10.1186/s12885-021-07996-1

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY