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. 2022 Jul 22:12:914156.
doi: 10.3389/fonc.2022.914156. eCollection 2022.

Alpha2beta1 Integrin Polymorphism in Diffuse Astrocytoma Patients

Silvia A Teixeira  1   2 , Regislaine V Burim  1   3 , Mariano S Viapiano  4   5 , Lucas T Bidinotto  1   6   7 , Suely K Nagashi Marie  8 , Suzana M Fleury Malheiros  9 , Sueli M Oba-Shinjo  10 , Augusto F Andrade  11 , Carlos G Carlotti  1
Affiliations

Alpha2beta1 Integrin Polymorphism in Diffuse Astrocytoma Patients

Silvia A Teixeira et al. Front Oncol. .

Abstract

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 α2β1 with the incidence of diffusely infiltrating astrocytoma and the progression of these tumors. Single-nucleotide polymorphism in intron 7 of the integrin ITGA2 gene was examined in 158 patients and 162 controls using polymerase chain reaction and restriction enzyme analysis. The ITGA2 genotype +/+ (with a BglII restriction site in both alleles) exhibited higher frequency in grade II astrocytoma compared to control (P = 0.02) whereas the genotype -/- (lacking the BglII site) correlated with the poorest survival rate (P = 0.04). In addition, in silico analyses of ITGA2 expression from low-grade gliomas (LGG, n = 515) and glioblastomas (GBM, n = 159) indicated that the higher expression of ITGA2 in LGG was associated with poor overall survival (P < 0.0001). However, the distribution of integrin ITGA2 BglII 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.

Keywords: ITGA2; brain microenvironment; extracellular matrix; invasion; low grade glioma; single nucleotide polymorphism; tumor progression.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
ITGA2 polymorphism genotyping by PCR-RFLP assay. This panel shows the BglII digestion of ITGA2 gene PCR products. Lane M: 100-bp molecular marker. Lanes 2, 3, 7, and 9 are representative of a homozygote -/- (absence of BglII site); lanes 1, 4, 5, 6, 8, 10, and 11 of a heterozygote -/+; and lane 12 of a homozygote polymorphic +/+ (presence of BglII site).
Figure 2
Figure 2
Kaplan–Meier curves of survival related to ITGA2 in (A) 515 patients LGG. LGG patients with high expression of ITGA2 had a poorer overall survival compared with patients with low expression and (B) 159 patients with GBM. The expression of ITGA2 in GBM was not statistically significant when compared with patients with low and high expressions and overall survival.
Figure 3
Figure 3
Kaplan–Meier curves of survival related to ITGA2 polymorphisms in 28 patients with astrocytoma grade II. Patients with ITGA2 -/- had a poorer prognosis than patients with (A) ITGA2 +/+ or (B) ITGA2 +/+,+/-.
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