Integrated bioinformatics analysis shows integrin alpha 3 is a prognostic biomarker for pancreatic cancer.

Integrin subunit alpha 3 (ITGA3) expression correlates with the development and prognosis of human cancers. This study aimed to investigate the association of ITGA3 expression with pancreatic cancer (PCa) prognosis. The ITGA3 gene expression data were extracted from The Cancer Genome Atlas (TCGA) pancreatic adenocarcinoma (PAAD) cohort and 14 Gene Expression Omnibus microarray datasets. The differences in ITGA3 expression levels between tumor and non-tumor tissues were compared using the Mann-Whitney U test. Cox regression analysis and meta-analysis were performed to detect the association of ITGA3 expression with PCa prognosis. ITGA3 expression was higher in tumors than in controls. Tumors with advanced grades (3/4) had higher ITGA3 levels compared with early-grade tumors (1/2). The meta-analysis of the TCGA PAAD cohort and seven microarray datasets (GSE28735, GSE62452, GSE79668, GSE71729, GSE57495, GSE78229, and GSE21501) showed that ITGA3 was a prognostic biomarker in PCa (hazard ratio (HR) = 1.38, 95% confidence interval (CI) 1.26-1.51, p < 0.00001). Five ITGA3-related genes, including ITGB1 (HR = 1.6), ITGB5 (HR = 1.6), ITGB6 (HR = 1.6), LAMA3 (HR = 2.1), and CD9 (HR = 2.3), correlated with PCa prognosis significantly (p < 0.05). Functional enrichment analysis showed that ITGA3 was related to "hsa04151: PI3K-Akt signaling pathway" and "hsa04510: Focal adhesion." We concluded that high ITGA3 expression was a potential prognostic biomarker in PCa.

Integrin α3 negative podocytes: A gene expression study.

Integrin α3ß1 is a cell adhesion receptor widely expressed in epithelial cells. Pathogenic variants in the gene encoding the integrin α3 subunit ITGA3 lead to a syndrome including interstitial lung disease, nephrotic syndrome, and epidermolysis bullosa (ILNEB). Renal involvement mainly consists of glomerular disease caused by loss of adhesion between podocytes and the glomerular basement membrane. The aim of this study was to characterize the impact of loss of integrin α3 on human podocytes. ITGA3 was stably knocked-out in the human podocyte cell line AB8/13, designated as PodoA3-, and in human proximal tubule epithelial cell line HK2 using the targeted genome editing technique CRISPR/Cas9. Cell clones were characterized by Sanger sequencing, quantitative PCR, Western Blot and immunofluorescence staining. RNASeq of integrin α3 negative cells and controls was performed to identify differential gene expression patterns. Differentiated PodoA3- did not substantially change morphology and adhesion under standard culture conditions, but displayed significantly reduced spreading and adhesion when seed on laminin 511 in serum free medium. Gene expression studies demonstrated a distinct dysregulation of the adhesion network with downregulation of most integrin α3 interaction partners. In agreement with this, biological processes such as "extracellular matrix organization" and "cell differentiation" as well as KEGG pathways such as "ECM-receptor interaction", "focal adhesion" and the "PI3K-Akt signaling pathway" were significantly downregulated in human podocytes lacking the integrin α3 subunit.

Investigation of the Presence of Integrin Alpha-3 and Beta-1 Receptors on Tumor Tissue, Metastatic Lymph Node and Normal Tissue in Thyroid Cancer.

Objectives: The important roles of integrins in tumor invasion, migration and proliferation are well known. In this study, we investigated the presence of integrin α3 and ß1 receptors in tumor tissue, metastatic lymph node (LN) and normal thyroid tissue of patients diagnosed with thyroid cancer (TCa) and showed the prognostic and diagnostic value of these molecules as well as peptide-receptor. Methods: Sixty-one patients with TCa were included in this study. The presence of integrin α3 and ß1 expression was investigated by immunohistochemical methods from tumor tissue after total thyroidectomy. TNM system was used in tumor staging. The relationship between prognostic properties such as tumor size, LN metastasis, capsular invasion and the presence of integrin α3 and ß1 expression was investigated. Results: Classical type papillary TCa was the most common subtype in our study group with 31.1%. Integrin ß1 was expressed in 4.9% (n=3) of normal tissue, 57.4% (n=35) of tumor tissue and 16.4% (n=10) of metastatic LN; integrin α3 was expressed in 50.8% (n=31) of normal tissue, 67.2% (n=41) of tumor tissue and 9.8% (n=6) metastatic LN. Integrin ß1 expression was observed 21.3% (n=13), integrin α3 in 14.8% (n=9) and integrin α3 and ß1 expression in 36.1% (n=22). Integrin ß1 expression increased statistically significantly in the presence of LN metastasis and capsular invasion (p=0.022, 0.014, respectively). Furthermore, the expression of integrin α3 was found to be statistically significant in primary tumors of patients with LN metastasis (p=0.045). Conclusion: Our study showed a significant increase in integrin α3 and ß1 expression in LN metastasis or thyroid capsule invasion in tumor. Thus, it appears that the demonstration of the presence of integrin α3 and ß1 expression in TCa is not only a prognostic biomarker but also has value as a potential theranostic target with peptide-bound radioactive agents.

Expression of CD151/Tspan24 and integrin alpha 3 complex in aid of prognostication of HER2-negative high-grade ductal carcinoma in situ.

The pro-tumorigenic and pro-metastatic functions of the tetraspanin protein CD151 (Tspan24) are thought to be dependent on its ability to form complexes with laminin-binding integrin receptors (i.e. alpha6beta1, alpha3beta1, alpha6beta4). We have previously reported that in invasive ductal carcinoma (IDC), CD151/alpha3beta1 complex was of prognostic value in patients with HER2-negative tumors. Extrapolating these findings to the pre-invasive setting, we aimed to make an assessment of a potential relationship between expression of the CD151/alpha3beta1 complex in DCIS and Van Nuys prognostic index (VNPI) in high-grade ductal carcinoma in situ (DCIS) in relation to the HER2 status. Protein distributions were analyzed in 49 samples of pure DCIS using immunohistochemistry. For each case immunoreactivity was assessed in at least 5 ducts (325 ducts in total) and an average score was taken for statistical analyses. When analyzed in the whole cohort, there was no statistical association between the VNPI and any of the proteins scored either separately or in combination. When stratified according to the HER2 status, in the HER2-negative subgroup, CD151 assessed in combination with alpha3beta1 was significantly correlated with VNPI (P = 0.044), while neither protein analyzed individually showed any significant link with the prognostic index. Expression of the CD151/alpha3beta1 complex in HER2-negative DCIS might reflect tumor behavior relevant to the patient outcome and thus might aid prognostication of the disease.

Expression of CD151 c-Met, integrin alpha 3, alpha 6 and the prognostic significance in pancreatic ductal adenocarcinoma / 中华胰腺病杂志

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.

Protective effect of astragaloside Ⅳ on high glucose-induced podocyte adhesion and its mechanism / 中华肾脏病杂志

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.

The expressions of integrin alpha 3 and MMP-9 in pancreatic adenocarcinoma and their association with clinical pathological characteristics / 肿瘤

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.