Integrin Alpha-2 as a Potential Prognostic and Predictive Biomarker for Patients With Lower-Grade Glioma

Abstract

Diffuse gliomas are the most common malignant brain tumors with the highest mortality and recurrence rate in adults. Integrin alpha-2 (ITGA2) is involved in a series of biological processes, including cell adhesion, stemness regulation, angiogenesis, and immune/blood cell functions. The role of ITGA2 in lower-grade gliomas (LGGs) is not well defined. Firstly, we downloaded RNA sequencing and relevant clinical information from The Cancer Genome Atlas cohort, the Chinese Glioma Genome Atlas cohort, and related immune cohorts. Next, prognosis analysis, difference analysis, clinical model construction, enrichment analysis, and immune infiltration analysis are performed for this study. These analyses indicated that ITGA2 may have clinical application value and research value in LGG immunotherapy. We also detected the mRNA and protein expression of ITGA2 in three LGG cell lines and normal glial cells using quantitative real-time polymerase chain reaction assay and western blot assay. Our study not only offers a novel target for LGG immunotherapy but also can better comprehend the mechanism of the development and progression of patients with LGG. This study revealed that ITGA2 may be a potential prognostic and predictive biomarker for LGG, which can bring new insights into targeted immunotherapy.

Alpha2beta1 Integrin Polymorphism in Diffuse Astrocytoma Patients

“…The poor prognosis for patients with LGG shows the diversity of this malignant glioma; therefore, new treatment strategies are needed to continuously improve the prognosis of LGG patients. Similar results to LGG have been described in a series of systematic analysis (68). In another study, the high expression of ITGA2 was associated with reduced survival rate of solid LGG patients with high expression of ITGA2 had a poorer overall survival compared with patients with low expression and (B) 159 patients with GBM.…”

“…cancer (28). The high expression of ITGA2 has been associated with worse prognosis (68), and studies have shown that multiple epigenetic mechanisms regulate ITGA2 expression in solid tumors including altered promoter methylation (50,69,70). In our results, low ITGA2 expression indicates an association with mutation in IDH, methylation in MGMT in mesenchymal-like tumors, and absence of mutation in TERT and G-CIMP and proneural tumors.…”

“…In another study, the authors reported that ITGA2 increased the PD-L1 expression in multiple types of cancer cells and improved the antitumor efficacy of immune therapy (27). Furthermore, immune checkpoint treatment has become a new method to treat cancer and ITGA2 can bring new insights into targeted immunotherapy and, for patient with LGG, may represent a potential molecular marker for targeted therapy (68). Therefore, it is very pivotal to find a new prognostic biomarker to enhance the treatment of glioma and increase the understanding of glioma treatment.…”

Radiomic profiling for insular diffuse glioma stratification with distinct biologic pathway activities

“…37 Finally, the results of the radiogenomic analysis indicated that 38 Multiple integrin family members have been reported as potential predictive biomarkers for survival in glioma patients. 39,40 P53 and VEGF-related mechanisms play a major role in the proliferation pathway. The targeted fusion protein combined with p53 induces the upregulation of p21 and p16 and inhibits the expression of CDK4 and phospho-Rb, thereby exerting the function of p53 in inhibiting the proliferation and migration of glioma cells.…”

“…Integrin expression is upregulated in various tumor tissues, including GBM, and promotes tumor cell migration and invasion, angiogenesis, and epithelial–mesenchymal transition (EMT) 38 . Multiple integrin family members have been reported as potential predictive biomarkers for survival in glioma patients 39,40 . P53 and VEGF‐related mechanisms play a major role in the proliferation pathway.…”