AUTHOR=Teixeira Silvia A. , Burim Regislaine V. , Viapiano Mariano S. , Bidinotto Lucas T. , Nagashi Marie Suely K. , Fleury Malheiros Suzana M. , Oba-Shinjo Sueli M. , Andrade Augusto F. , Carlotti Carlos G. 

TITLE=Alpha2beta1 Integrin Polymorphism in Diffuse Astrocytoma Patients

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.914156

DOI=10.3389/fonc.2022.914156

ISSN=2234-943X

ABSTRACT=<p>Integrins are heterodimeric transmembrane glycoproteins resulting from the non-covalent association of an α and β chain. The major integrin receptor for collagen/laminin, α2β1 is expressed on a wide variety of cell types and plays an essential role in the adhesion of normal and tumor cells to the extracellular matrix. Integrin-triggered signaling pathways promote the invasion and survival of glioma cells by modifying the brain microenvironment. In this study, we investigated the association of a specific genetic polymorphism of integrin <italic>α2β1</italic> with the incidence of diffusely infiltrating astrocytoma and the progression of these tumors. Single-nucleotide polymorphism in intron 7 of the integrin <italic>ITGA2</italic> gene was examined in 158 patients and 162 controls using polymerase chain reaction and restriction enzyme analysis. The <italic>ITGA2</italic> genotype +/+ (with a <italic>Bgl</italic>II restriction site in both alleles) exhibited higher frequency in grade II astrocytoma compared to control (P = 0.02) whereas the genotype -/- (lacking the <italic>Bgl</italic>II site) correlated with the poorest survival rate (P = 0.04). In addition, <italic>in silico</italic> analyses of <italic>ITGA2</italic> expression from low-grade gliomas (LGG, n = 515) and glioblastomas (GBM, n = 159) indicated that the higher expression of <italic>ITGA2</italic> in LGG was associated with poor overall survival (P &lt; 0.0001). However, the distribution of integrin <italic>ITGA2 Bgl</italic>II genotypes (+/+, +/-, -/-) was not significantly different between astrocytoma subgroups III and IV (P = 0.65, 0.24 and 0.33; 0.29, 0.48, 0.25, respectively) compared to control. These results suggest a narrow association between the presence of this SNP and indicate that further studies with larger samples are warranted to analyze the relation between tumor grade and overall survival, highlighting the importance of determining these polymorphisms for prognosis of astrocytomas.</p>