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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.
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Objective To investigate the expression and prognostic significance of CD151, c-Met and integrin alpha 3, alpha6 in pancreatic ductal adenocarcinoma (PDAC). Methods The expression of CD151, c-Met and integrin alpha3, alpha6 in 71 patients with PDAC and 10 samples of normal pancreas tissues were detected by immunohistochemistry, and the relationship between the expression of CD151, c-Met and integrin alpha 3, alpha 6 and the clinicopathological features, prognosis of these patients was analyzed. Results The positive expression rates of CD151, c-Met and integrin alpha 3, alpha 6 in PDAC were 81.69% (58/71) , 69.01% (49/71), 69.01% (49/71) and 84.51% (60/71) , and there was no expression in normal pancreas tissues. The expressions of CD151, c-Met were significantly associated with TNM stage and lymph node metastasis (P < 0.05). The expression of CD151 was positively correlated with the expressions of c-Met and integrin alpha3, alpha6 (r =0.583, P =0.000, r = 0.457;P =0.000, r = 0.671 ;P =0.000). Univariate analysis suggested the expression of CD151, c-Met and integrin alpha3, alpha6 was associated with survival (P<0.05). Multivariate analysis suggested the expression of CD151, c-Met was the independent prognostic factor for post-operative survival. Conclusions CD151, c-Met and integrin alpha3, alpha6 play a role in the development, metastasis and prognosis of PDAC, and they might be new markers to predict biological behavior and the prognosis of PDAC patients.
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ObjectiveTo study the effect of astragaloside Ⅳ(AS-Ⅳ) on glucose-induced podocyte adhesion and its possible mechanism. MethodsConditionally immortalized mouse podoeytes were treated with 10, 50, 100 mg/L AS-Ⅳ and with 100 mg/L AS-Ⅳ for 3, 6, 12, 24 h. Cell attachment was measured by fluorescence and centrifugation cell adhesion assays, respectively. Expression of α3β1 integrin mRNA and protein was examined by real-time PCR and Western blot. ResultsHigh glucose induced a significant reduction in adherent podocytes compared to normal glucose group (P<0.05). AS-Ⅳ improved high glucose-induced podocyte adhesion in a time- and dose-dependent manner. Real-time PCR and Western blot analysis revealed that high glucose-induced down-regulation of α3β1 integrin in podocytes were significantly meliorated by AS-Ⅳ (P<0.05). ConclusionAstragaloside Ⅳ improved high glucose-induced podocyte adhesion which may be mediated through α3β1 integrin up-regulation.
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Objective: To detect the expressions of integrin alpha 3 and matrix metalloproteinase-9 (MMP-9) in pancreatic adenocarcinoma, and investigate their relationahip with clinicopathological parameters, furthermore analyze the correlation between integrin alpha 3 and MMP-9. Methods: We collected 100 cases of paraffin-embedded pancreatic adenocarcinoma tissues. The expressions of integrin alpha3 and MMP-9 were detected by immunohistochemical labelled streptavidin biotin ( LsAB) methods. Results: Ninety eight percent pancreatic adenocarcinomas were integrin alpha3-positive and 75% pancreatic adenocarcinomas highly expressed integrin alpha 3. The expressions of integrin alpha 3 in head, neck and uncinate pancreatic adenocarcinomas were stronger than those in pancreatic adenocarcinomas located at body and tail (P=0.041). Increased expression of integrin alpha3 was associated with local lymph node metastasis (P=0.012). Eighty one percent pancreatic adenocarcinomas expressed MMP-9 and 39% of them showed strongly positive. There was no correlation between the expression of MMP-9 and age, gender, tumor location, tumor grade, duodenum invasion, local lymph node metastasis, perineural invasion or TNM stage. The expression of MMP-9 positively correlated with the expression of integrin alpha 3. Conclusion: Expression of integrin alpha 3 correlates with the location of pancreatic adenocarcinomas and plays a role in local lymph node metastasis. Integrin alpha 3 might up-regulate the expression of MMP-9.