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

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 tumors remain unclear.Methods: The 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.Results: ITGA5 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”.Conclutions: Our 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.

Identification of differentially expressed genes and pathways for risk stratification in HPV-associated cancers governing different anatomical sites

“…LAMB combines with LAMC; together, they initiate cell assembly to promote cancer invasion and gene expression in various invasive cancers, including LAMB1 gene expression in head and neck, liver, and uterine endometrial cancers, and LAMC1 gene expression in gastric cancer [28][29][30]. Integrin subunits α5 and β1 primarily conjoin to form α5β1 heterodimers, and ITGA5 and ITGB1, the genes encoding α5 and β1, respectively have been suggested to be associated with tumor aggressive behavior, such as cancer progression and treatment resistance [31,32]. In our study, an increase in ITGA5 and ITGB1 expression was characteristically identified in highrisk HPV (+) and HPV (-) groups in HNC, and was associated with the worsening OS in both HPV-related HNC and CC.…”

Comprehensive Analysis on the Expression and Prognostic value of ITGA Family in Human Pancreatic Adenocarcinoma

“…Besides, ITGA4 has also been found highly expressed in chronic lymphocytic leukemia [45], and colorectal tumors [46]. Upregulation of ITGA5 was detected in gastric cancer [47]. ITGA7 was markedly up-regulated in breast cancer [48], prostate cancer [49], and non-small-cell lung cancer [50].…”

A neural‐related gene risk score for head and neck squamous cell carcinoma

“…Integrin α5 (ITGA5) primarily binds to integrin β1 to form α5β1-integrin [9], which is highly expressed on the developing axons, the regenerating neurites and Schwann cells within the injured nerves, and performs vital functions in neural development and regeneration [24]. Meanwhile, ITGA5 overexpressed in multiple types of cancer and is essential for aggressive behaviors of tumors, including HNSCC [53]. Muscle glycogen phosphorylase or myophosphorylase (PYGM) is considered as a key enzyme in glycogen degradation existing in the muscular system and astrocytes in the central nervous system [14,33].…”