Integrin alpha 3 expression in glioma and its prognostic value in glioma patients
10.3760/cma.j.cn115354-20211012-00654
- VernacularTitle:ITGA3在脑胶质瘤中的表达及其对预后的评估价值
- Author:
Xiang ZHOU
1
;
Zhongwei WANG
;
Haigang CHANG
;
Shupeng ZHAO
;
Baozhe JIN
Author Information
1. 新乡医学院第一附属医院神经外科，卫辉 453100
- Keywords:
Glioma;
Integrin alpha 3;
Differential expression;
Prognosis
- From:
Chinese Journal of Neuromedicine
2022;21(3):232-241
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the differences of integral alpha 3 (ITGA3) mRNA and protein expressions in gliomas of different grades and different cell lines, and gliomas tissues of different clinical and molecular characteristics, and evaluate their prognostic values in brain glioma patients.Methods:(1) ITGA3 mRNA expression data in the brain gliomas and clinical data of these glioma patients were obtained from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA). The differences of ITGA3 mRNA expressions in glioma patients with different gender, ages, WHO grading, isocitrate dehydrogenase 1 ( IDH) mutation statuses, and 1p/19q co-deletion statuses were compared. Kaplan-Meier method was used to plot and compare the survival curves of patients with ITGA3 mRNA high expression and ITGA3 mRNA low expression. Receiver operating characteristic (ROC) curve was used to analyze the predictive efficiency of ITGA3 mRNA expression in survival rate of gliomas. Univariate and multivariate Cox regression analyses were used to explore the independent influencing factors for prognoses in glioma patients. The independent influencing factors for prognosis were used to construct nomograms and the calibration diagram was used to verify the reliability of nomograms in predicting the prognoses of these patients. (2) Intracellular localization of ITGA3 and ITGA3 protein expression in low- and high-grade gliomas were determined by on-line database of Human Protein Atlas (HPA). (3) Brain glioma cells U87, U118, U251 and human astrocytes SVG were cultured in vitro, and the ITGA3 mRNA and protein expressions in cells were detected by Western blotting and reverse transcription (RT)-PCR, respectively. Results:(1) In TCGA database, the ITGA3 mRNA expressions in gliomas of WHO grading II, III and IV increased successively, with significant differences (P<0.05). In CGGA database, the ITGA3 mRNA expression in glioma of WHO grading IV was statistically higher than that in glioma of WHO grading II and III ( P<0.05). In TCGA and CGGA databases, the ITGA3 mRNA expressions in glioma patients aged ≤40 years and >40 years, patients with IDH wild-type and IDH mutation, and patients with chromosome 1p/19q deletion and chromosome 1p/19q non-deletion were statistically different ( P<0.05). The survival rate of patients with low ITGA3 mRNA expression was significantly higher than that of patients with high ITGA3 mRNA expression, no matter in low-grade glioma, glioblastoma, or entire glioma samples ( P<0.05). ROC curve showed that, in TCGA database, the area under the curve (AUC) of ITGA3 mRNA in predicting 1, 3, and 5 years survival was 0.791, 0.786, and 0.708 in glioma patients; in CGGA database, the AUC of ITGA3 mRNA in predicting 1, 3, and 5 years survival was 0.661, 0.667, and 0.659. Multivariate Cox regression analysis showed that, in TCGA database, age, WHO grading, IDH mutation, chromosome 1p/19q deletion and ITGA3 mRNA expression ( HR=1.018, 95%CI: 1.006-1.030, P=0.0.003) were independent influencing factors for prognoses of glioma patients ( P<0.05); and in CGGA database, WHO grading, IDH mutation, chromosome 1p/19q deletion, and ITGA3 mRNA expression ( HR=1.445, 95%CI: 1.132-1.844, P=0.003) were independent influencing factors for prognoses of glioma patients ( P<0.05). Nomograms showed that age had the greatest influence in survival, followed by ITGA3 mRNA expression. Calibration plots showed that nomogram was reliable in predicting 1-, 3-, and 5-year survival in glioma patients. (2) Immunofluorescence localization showed that ITGA3 protein mainly aggregated in cell membrane and vesicles. Immunohistochemical staining showed that the ITGA3 protein expression in high-grade glioma tissues was obviously higher than that in low-grade glioma tissues. (3) The results of RT-PCR and Western blotting revealed that the ITGA3 mRNA and protein expressions in glioma cell lines U87, U118 and U251 were significantly higher than those in SVG cells ( P<0.05). Conclusion:The ITGA3 mRNA and protein expression levels are correlated with the malignant degrees of glioma; patients with ITGA3 mRNA low expression tend to have a high overall survival; ITGA3 mRNA expression can be used as an index to evaluate the prognoses of glioma patients.
