ITGA5 Is a Novel Oncogenic Biomarker and Correlates With Tumor Immune Microenvironment in Gliomas

Abstract

Gliomas are the most aggressive primary intracranial malignancies with poor overall survival. ITGA5 is one member of the integrin adhesion molecule family and is implicated in cancer metastasis and oncogenesis. However, few studies have explored the association between tumor immune microenvironment and ITGA5 expression level in gliomas. Firstly, we analyzed 3,047 glioma patient samples collected from the TCGA, the CGGA, and the GEO databases, proving that high ITGA5 expression positively related to aggressive clinicopathological features and poor survival in glioma patients. Then, based on the ITGA5 level, immunological characteristics and genomic alteration were explored through multiple algorithms. We observed that ITGA5 was involved in pivotal oncological pathways, immune-related processes, and distinct typical genomic alterations in gliomas. Notably, ITGA5 was found to engage in remolding glioma immune infiltration and immune microenvironment, manifested by higher immune cell infiltration when ITGA5 is highly expressed. We also demonstrated a strong correlation between ITGA5 and immune checkpoint molecules that may be beneficial from immune checkpoint blockade strategies. In addition, ITGA5 was found to be a robust and sensitive indicator for plenty of chemotherapy drugs through drug sensitivity prediction. Altogether, our comprehensive analyses deciphered the prognostic, immunological, and therapeutic value of ITGA5 in glioma, thus improving individual and precise therapy for combating gliomas.

Adipose Tissue-Derived Stem Cell Extracellular Vesicles Suppress Glioblastoma Proliferation, Invasiveness and Angiogenesis

“…ITGa5 forms a complex with ITGβ1 and is responsible for tumour cell migration and invasion. According to a recent study, this gene is involved in essential oncological pathways and is responsible for typical genomic alterations in gliomas, including the tumour immune microenvironment formation [53]. ITGβ1 showed a strong trend to be downregulated by ASC-EVs in U87 MG.…”

DDOST Correlated with Malignancies and Immune Microenvironment in Gliomas

“…Researching the molecular biomarkers and unique immunological status of gliomas has a profound effect on cancer diagnosis and therapeutic strategies. New studies have found that some biomarkers, such as ITGA-5 and Tenascin-C, could predict glioma prognosis, and are closely related to the immunosuppressive microenvironment, particularly for the clinical application of immunotherapy in glioma ( 26 , 27 ). New studies also reported that DDOST could interact with the microenvironment of gliomas and was negatively related to tumor-infiltrating B cells and CD4+ T cells and positively related to CAFs and tumor-associated macrophages (TAMs).…”

Construction of a prognostic classifier and prediction of the immune landscape and immunosuppressive molecules in gliomas based on combination of inflammatory response-related genes and angiogenesis-associated genes

“…ITGA5 also tightly connect with IC molecules, which may benefit from IC blockade strategies. 50 Lysosome associated membrane glycoprotein 3 (LAMP3), belonging to the LAMP protein family, is overexpressed in a variety of cancers in which it is related to an unsatisfactory prognosis and may be pivotal for tumor metastasis. 51 Matrix metalloproteinase 14 (MMP14) is a membrane-type MMP, and the enhanced MMP14 activity is frequently associated with malignancy and is thought to promote metastasis.…”