Dataset Information

Biological and Clinical Significance of GATA3 Detected from TCGA Database and FFPE Sample in Bladder Cancer Patients.

ABSTRACT: Purpose:The purpose of the present study was to investigate the biological and clinical significance of GATA binding protein 3 (GATA3) in bladder cancer patients. Patients and Methods:For the detection of the correlation between GATA3 expression and bladder cancer, we downloaded the mRNA expression data from the Cancer Genome Atlas (TCGA) database and conducted immunohistochemistry staining on formalin-fixed paraffin-embedded (FFPE) sample tissues. Then, bladder cancer cell lines were utilized to investigate the potential functions of GATA3 by cell apoptosis, proliferation and cycle assays. Results:The mRNA data from TCGA database and bladder cancer cell lines suggested that GATA3 mRNA expression was significantly higher compared with normal tissues and cells. Conversely, the Western blot assay revealed that the expression of GATA3 was significantly lower in bladder cancer than normal urothelial cell line. Additionally, we found that over-expression of GATA3 was significantly associated with tumor subtype (P = 0.001 in TCGA; P = 0.004 in FFPE tissues), earlier clinical stage (P < 0.001 in TCGA; P < 0.001 in FFPE) and lower grade tumor (P = 0.057 in TCGA; P = 0.002 in FFPE). Kaplan-Meier analysis and multivariate Cox regression analysis indicated that age (P < 0.001 in both cohort), clinical stage (P = 0.028 in TCGA; P = 0.011 in FFPE), recurrence (P < 0.001) and low GATA3 in TCGA cohort (P = 0.035) but high GATA3 in FFPE cohort (P = 0.033) were independent risk factors for overall survival in patients. The assay to detect potential functions of GATA3 indicated that this biomarker could arrest the cell cycle of G2/M and S phase in T24 cells, and inhibit bladder cancer cells proliferation. Conclusion:Collectively, our findings identified that GATA3 served as an important prognosis biomarker for bladder cancer patients. However, the mechanism of GATA3 in bladder cancer deserves further studies.

SUBMITTER: Wang C

PROVIDER: S-EPMC6999784 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Biological and Clinical Significance of GATA3 Detected from TCGA Database and FFPE Sample in Bladder Cancer Patients.

Wang Chenglu C Yang Shuang S Jin Lu L Dai Guangcheng G Yao Qiu Q Xiang Han H Zhang Yongsheng Y Liu Xiaolong X Xue Boxin B

OncoTargets and therapy 20200131

<h4>Purpose</h4>The purpose of the present study was to investigate the biological and clinical significance of GATA binding protein 3 (GATA3) in bladder cancer patients.<h4>Patients and methods</h4>For the detection of the correlation between GATA3 expression and bladder cancer, we downloaded the mRNA expression data from the Cancer Genome Atlas (TCGA) database and conducted immunohistochemistry staining on formalin-fixed paraffin-embedded (FFPE) sample tissues. Then, bladder cancer cell lines ...[more]

PMID: 32099398

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Project description:BackgroundBladder cancer (BCa) is a common urothelial malignancy. The Cancer Genome Atlas (TCGA) database allows for an opportunity to analyze the relationship between gene expression and clinical outcomes in bladder cancer patients. This study is aimed at identifying prognosis-related genes in the bladder cancer microenvironment.MethodsImmune scores and stromal scores were calculated by applying the ESTIMATE algorithm. We divided bladder cancer patients into high and low groups based on their immune/stromal scores. Then, differentially expressed genes (DEGs) were identified in bladder cancer patients based on the TCGA database. We evaluated the correlation between immune/stromal scores and clinical characteristics as well as prognosis. Finally, we validated identified genes associated with bladder cancer prognosis through a cohort study in the Gene Expression Omnibus (GEO) database.ResultsA higher stromal score was associated with female (vs. malep = 0.037), age > 65 (vs.age ≤ 65 p = 0.015), T3/4 (vs. T1/2,p < 0.001), N status(p = 0.016), and pathological high grade (vs. low gradeP < 0.001). By analyzing DEGs, there were 1125 genes commonly upregulated, and 209 genes were commonly downregulated. Protein-protein interaction networks further showed the important protein that may be involved in the biological behavior and prognosis of BCa, such as FN1, CXCL12, CD3E, LCK, and ZAP70. A total of 14 DEGs were found to be associated with overall survival of bladder cancer. After validation by a cohort of 165 BCa cases with detailed follow-up information from GSE13507, 10 immune-associated DEGs were demonstrated to be predictive of prognosis in BCa. Among them, 5 genes have not been reported previously associated with the prognosis of BCa, including BTBD16, OLFML2B, PRRX1, SPINK4, and SPON2.ConclusionsOur study elucidated tight associations between stromal score and clinical characteristics as well as prognosis in BCa. Moreover, we obtained a group of genes closely related to the prognosis of BCa in the tumor microenvironment.

Project description:BackgroundEstrogen receptors alpha (ERα) and beta (ERβ) and the cooperating protein GATA-binding factor 3 (GATA3) have been implicated in bladder carcinogenesis and tumour progression. GATA3 and ER have been functionally linked in the establishment of luminal fate in breast tissue, but to date their relationship in bladder cancer has not been established. This information will be useful to advance diagnostic and prognostic markers.AimTo determine the relationship between the expression of ERα, ERβ and GATA3 in bladder cancer, disclose their prognostic and diagnostic value and their association with clinicopathological characteristics.MethodsA comprehensive literature search in PubMed database was performed for all immunohistochemical studies of ERα, ERβ and/or GATA3 in bladder cancer patients. We selected eligible studies in accordance with the PRISMA guidelines and evaluated methodological quality and risk of bias based on quality criteria from the reporting recommendations for tumour MARKer (REMARK) prognostic studies. Risk of bias assessment was performed using Review Manager 5. R software was used for all statistical analysis, the packages used were meta and dmetar for the standard meta-analysis, and netmeta for the network meta-analysis.ResultsThirteen studies were eligible for ERα, 5 for ERβ and 58 for GATA3 meta-analysis. Low grade tumours showed significantly lower ERα expression. GATA3 was widely expressed in bladder tumours, especially urothelial carcinomas, with higher expression of GATA3 in low grade and low stage tumours. Data was insufficient to determine the prognostic value of either ERα or ERβ, but GATA3-positivity was associated with higher recurrence free survival. A negative correlation between ERα or ERβ positivity and GATA3 expression was disclosed. Additionally, several sources of heterogeneity were identified, which can be used to improve future studies.ConclusionThe clinicopathological value of ERα and ERβ was inconclusive due to low availability of studies using validated antibodies. Still, this meta-analysis supports GATA3 as good prognostic marker. On the contrary, ERα-positivity was associated to higher grade tumours; while ERα and ERβ were inversely correlated with GATA3 expression. Considering that it has previously been shown that bladder cancer cell lines have functional ERs, this suggests that ERα could be activated in less differentiated cells and independently of GATA3. Therefore, a comprehensive analysis of ERα and ERβ expression in BlaCa supported by complete patient clinical history is required for the identification of BlaCa subtypes and subgroups of patients expressing ERα, to investigate if they could benefit from treatment with hormonal therapy.Systematic review registrationProspero, CRD42021226836.

Project description:BackgroundMuscular invasive bladder cancer (MIBC) is a common malignant tumor in the world. Because of their heterogeneity in prognosis and response to treatment, biomarkers that can predict survival or help make treatment decisions in patients with MIBC are essential for individualized treatment.AimWe aimed to integrate bioinformatics research methods to identify a set of effective biomarkers capable of predicting, diagnosing, and treating MIBC. To provide a new theoretical basis for the diagnosis and treatment of bladder cancer.Methods and resultsGene expression profiles and clinical data of MIBC were obtained by downloading from the Cancer Genome Atlas database. A dataset of 129 MIBC cases and controls was included. 2084 up-regulated genes and 2961 down-regulated genes were identified by differentially expressed gene (DEG) analysis. Then, gene ontology analysis was performed to explore the biological functions of DEGs, respectively. The up-regulated DEGs are mainly enriched in epidermal cell differentiation, mitotic nuclear division, and so forth. They are also involved in the cell cycle, p53 signaling pathway, PPAR signaling pathway, and so forth. The weighted gene co-expression network analysis yielded five modules related to pathological stages and grading, of which blue and turquoise were the most relevant modules for MIBC. Next, Using Kaplan-Meier survival analysis to identify further hub genes, the screening criteria at p ≤ .05, we found CNKSR1, HIP1R, CFL2, TPM1, CSRP1, SYNM, POPDC2, PJA2, and RBBP8NL genes associated with the progression and prognosis of MIBC patients. Finally, immunohistochemistry experiments further confirmed that CNKSR1 plays a vital role in the tumorigenic context of MIBC.ConclusionThe research suggests that CNKSR1, POPDC2, and PJA2 may be novel biomarkers as therapeutic targets for MIBC, especially we used immunohistochemical further to validate CNKSR1 as a therapeutic target for MIBC which may help to improve the prognosis for MIBC.

Dataset Information

Biological and Clinical Significance of GATA3 Detected from TCGA Database and FFPE Sample in Bladder Cancer Patients.

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Biological and Clinical Significance of GATA3 Detected from TCGA Database and FFPE Sample in Bladder Cancer Patients.

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