GATA Binding Protein 3 Expression Research Articles

Association of GATA3 expression in triple-positive breast cancer with overall survival and immune cell infiltration

Breast cancer remains a leading cause of cancer-related mortality among women, with triple-positive breast cancer (TPBC) being a particularly aggressive subtype. GATA binding protein 3 (GATA3) plays a crucial role in the luminal differentiation of breast epithelium and T-cell differentiation. However, the relationship between GATA3 and immune infiltration in TPBC remains unclear. This study collected and analyzed TPBC data from The Cancer Genome Atlas (TCGA), METABRIC, and GSE123845 databases. Univariate and multivariate Cox regression analyses, along with Kaplan–Meier survival analyses, were employed to assess the prognostic value of GATA3 and other clinical features. Subsequently, Gene Set Enrichment Analysis (GSEA) was conducted to explore the potential biological functions and regulatory mechanisms of GATA3 in TPBC. Additionally, ssGSEA analysis revealed the connection between GATA3 and immune infiltration. And the effects of neoadjuvant chemotherapy and immunotherapy on GATA3 expression were also explored. Finally, clinical samples were used to detect the relationship between GATA3 expression and tumor infiltrating lymphocyte (TIL) levels. Our results demonstrated that GATA3 was significantly overexpressed in TPBC tissues compared to normal tissues (P < 0.05). A positive correlation between GATA3 mRNA and protein levels was observed (R = 0.55, P < 0.05). Notably, high GATA3 expression was associated with poor overall survival (HR = 1.24, 95% confidence interval (CI) 1.25–11.76, P < 0.05). GSEA indicated significant enrichment of immune-related gene sets in low GATA3 expression groups. Furthermore, pathologic complete response (pCR) patients exhibited significantly lower GATA3 expression compared to residual disease (RD) patients. Mutation analysis revealed higher PIK3CA and TP53 mutation rates in high GATA3 expression groups. Finally, clinical validation data showed that the degree of TILs was significantly higher in the low GATA3 expression group. In conclusion, this study suggests that high GATA3 expression may be associated with poor prognosis and may reduce immune infiltration in TPBC.

Increased level of GATA3-AS1 long non-coding RNA is correlated with the upregulation of GATA3 and IL-4 genes in multiple sclerosis patients.

Long non-coding RNAs (lncRNAs) play various roles in gene regulation. GATA3 antisense RNA 1 (GATA3-AS1) is an lncRNA gene neighboring GATA binding protein 3 (GATA3). The current study aims to quantitatively compare the levels of the expression of GATA3-AS1, GATA3, and Interleukin-4 (IL-4) in peripheral blood mononuclear cells (PBMC) samples of MS patients and healthy individuals under the hypothesis of regulation of GATA3 and IL-4 expression orchestrated by GATA3-AS1. In this case-control study, the GATA3-AS1, GATA3 and IL-4 expression profiles were assessed using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Also, we assessed the IL-4 levels in the serum. The median fold changes in MS patients vs. controls were (4.39 ± 0.38 vs. 2.44 ± 0.20) for GATA3-AS1, (5.22 ± 0.51 vs. 2.86 ± 0.30) for GATA3, and (6.16 ± 0.52 vs. 3.57 ± 0.38) for IL-4, (P < 0.001). Furthermore, the mean serum levels of IL-4 were 30.85 ± 1.53 pg/ml in MS patients and 11.15 ± 4.23 pg/ml in healthy controls (P < 0.001). ROC curve analysis showed that the level of GATA3-AS1 might serve as a biomarker for diagnosing MS patients with the area under the curve (AUC = 0.918, P < 0.0001). Based on our results, this GATA3-AS1/GATA3/IL-4 pathway may increase IL-4 expression in MS patients. Our results indicate a probably regulatory function for GATA3-AS1and the levels of GATA3-AS1 in blood could be important biomarkers for MS diagnosis. To confirm and be more certain of these results, it is necessary to study neuromyelitis optica (NMO) and asthma patients in future studies.

Acupuncture at "Die E acupoint" alleviates inflammatory reaction via inhibiting TLR4/MyD88/NF-κB signaling in rats with allergic rhinitis.

To observe effects of acupuncture at "Die E acupoint" on the protein expression levels of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear transcription factor κB (NF-κB), transcription factor T-bet (T-bet), and GATA-binding protein-3 (GATA-3) in the nasal mucosa and the serum contents of related inflammatory cytokines in rats with allergic rhinitis, so as to explore the mechanism of acupuncture in treating allergic rhinitis. Twenty-four healthy SD rats were randomly divided into blank, model, acupuncture, and sham acupuncture groups, with 6 rats in each group. The rat model of allergic rhinitis was established by using ovalbumin induction. The rats in the acupuncture group received bilateral acupuncture at the "Die E acupoint" with a depth of 15-20 mm, while the rats in the sham acupuncture group received only sham acupuncture (light and shallow acupunture of the skin at the "Die E acupoint" ). Both interventions were performed once daily for a total of 6 days. Behavioral scores of rats in each group were recorded. Pathological changes of nasal mucosa were observed by H.E. staining. Serum contents of IgE, ovalbumin-specific IgE (OVA-sIgE), interferon(IFN)-γ, interleukin(IL)-4, IL-10 and IL-17 were measured by ELISA and the protein expression levels of T-bet, GATA-3, TLR4, MyD88 and NF-κB p65 in the nasal mucosa were detected by Western blot. After modeling, compared with the blank group, rats in the model group showed increased behavioral scores, serum IgE, OVA-sIgE, IL-4, and IL-17 contents, and nasal mucosal GATA-3, TLR4, MyD88, and NF-κB p65 protein expression levels (P<0.05), whereas the contents of serum IFN-γ, IL-10 and the protein expression level of T-bet in the nasal mucosa were decreased (P<0.05). Comparison between the EA and model groups showed that acupuncture intervention can decrease the behavioral scores of rats with allergic rhinitis, the contents of serum IgE, OVA-sIgE, IL-4, IL-17, and the protein expression levels of GATA-3, TLR4, MyD88, and NF-κB p65 in the nasal mucosa (P<0.05), and up-regulate the contents of serum IFN-γ, IL-10, and the nasal mucosal T-bet protein expression level. Sham acupuncture did not have a significant modulating effect on the above indicators. Inflammatory infiltration of nasal mucosa was seen in the model group and sham acupuncture, and the inflammatory reaction was milder in the acupuncture group. Acupuncture at "Die E acupoint" can alleviate the symptoms of allergic rhinitis and suppress the inflammation of nasal mucosa in rats, which may be related to inhibiting the TLR4/MyD88/NF-κB signaling and balancing the levels of cytokines of Th1/Th2 and Treg/Th17, and T-bet/GATA-3.

Absence of GATA3/FOXA1 co-expression predicts poor prognosis in upper tract urothelial carcinoma.

GATA binding protein 3 (GATA3) and forkhead box A1 (FOXA1) have been individually implicated in the progression of upper tract urothelial carcinoma (UTUC). This study aims to evaluate the prognostic value of GATA3/FOXA1 co-expression in UTUC patients. We collected 108 UTUC pathological tissue samples with complete follow-up data and 24 normal control urothelial tissues. We created a 132-site microarray and performed immunohistochemistry (IHC) to measure GATA3 and FOXA1 expression levels. Kaplan-Meier survival and Cox regression analyses were conducted to assess UTUC prognosis. GATA3 expression was positively correlated with FOXA1 (P=0.031). Absence of GATA3/FOXA1 co-expression (GATA3-/FOXA1-) was associated with tumor extensive necrosis (P=0.001) after Bonferroni correction for multiple comparisons. GATA3-/FOXA1- was associated with shorter Disease-Free Survival (DFS) (P=0.001) and Cancer-Specific Survival (CSS) (P<0.001) than other combination groups. Multivariate analyses identified extensive necrosis as an independent prognostic factor for CSS (P=0.030). Our study revealed a positive correlation between GATA3 and FOXA1 expression in UTUC. GATA3-/FOXA1- is linked to tumor extensive necrosis and poor prognosis in UTUC and may serve as a potential biomarker for UTUC patients.

A noninvasive method for the detection of foetal DNA in early pregnancy based on differential methylation pattern of Ras association domain family member 1A

Background The detection of foetal DNA and extravillus trophoblasts (EVTs) in early pregnancy in cervical and uterine samples offers a potential pathway for non-invasive prenatal diagnostics. However, the challenge lies in effectively quantifying these samples. This study introduces a novel approach using the Ras association domain family 1 A (RASSF1A), which exhibits hypermethylation in foetal cells and hypomethylation in maternal cells. The differential methylation pattern of RASSF1A provides a unique biomarker for quantifying foetal cells in cervical and intrauterine samples. Methods This study was conducted between September 2022 and May 2023. In total, 23 samples (12 cervical cell samples and 11 intrauterine samples) were collected from women in the Sichuan Jinxin Women & Children Hospital, Jingxiu District, Chengdu, China. The cervical cell samples were collected via lavage and brush techniques, and the intrauterine cell samples were obtained via uterine lavage. These samples were collected as part of a broader effort to advance our understanding of foetal cell dynamics during early pregnancy. The sampling methods were chosen for their minimally invasive nature and their potential in capturing a representative cell population from the respective sites. After digestion of the cell samples using a methylation-sensitive restriction enzyme cocktail, a critical step to differentiate between maternal and foetal DNA, the quantitative polymerase chain reaction (qPCR) of RASSF1A and β-actin (ACTB) were employed to measure foetal DNA and cell concentrations. Immunofluorescence techniques targeting histocompatibility complex, class I G (HLA-G) and GATA binding protein 3 (GATA-3) were employed to detect EVTs in the cell samples and in decidual tissue, with the latter providing an additional layer of confirmation for the presence of foetal cells. Results The results showed no hypermethylated RASSF1A was detected in any of the cervical samples, irrespective of whether the samples were obtained by brush or lavage. However, an average of 17,236 ± 7490 foetal cells per sample were detected in the uterine lavage samples. Foetal cells accounted for approximately 0.14% ± 0.10% of the total cell population in these samples. The presence of EVTs in these samples was confirmed by their expression of both HLA-G and GATA-3. Conclusion The detection of foetal cells in uterine cavity samples based on hypermethylation of RASSF1A and quantification of foetal cells can be used to prenatal screening. GATA-3 can be used to label EVTs.

Expression of Gata Binding Protein 3 as a Prognostic Factor in Urogenital Lesions and Its Association With Morphology.

Urogenital malignancies, encompassing urinary bladder cancer, prostate cancer, and renal cell carcinoma, pose significant diagnostic challenges due to overlapping histopathological features. GATA binding protein 3 (GATA3), a transcription factor associated with urothelial tissue, has shown promise as a potential diagnostic marker.This study aimed to investigate the incidence of these malignancies, explore GATA3's involvement in urothelial cancer (UC), and determine its role in distinguishing urogenital malignancies. A cross-sectional, retro-prospective, hospital-based study was conducted from May 2019 to April 2021. The surgical samples of patients who underwent transurethral resection of bladder tumour (TURBT), transurethral resection of the prostate (TURP), radical cystoprostatectomy, total and partial radical nephrectomy specimens during the study period were reviewed. Patients diagnosed with urinary bladder neoplasm and high-grade prostate neoplasm along with chromophobe, oncocytic, sarcomatoid variant and clear cell carcinoma, renalcell carcinoma were included. Immunohistochemical analysis of GATA3 expression was performed, with scoring based on nuclear staining intensity and percentage of tumor cells labeled. The study included 64 patients, predominantly males over 60 years. Personal habits revealed a high prevalence of smoking (85.9%). The most prevalent symptom was hematuria (75.0%), followed by hematuria with urgency (20.3%). The most common site of lesion was posterolateral (31.3%). Urothelial cancer was the most common malignancy, primarily high-grade. Strong positive GATA3 expression was significantly associated with high-grade UC (p=0.01) and invasion (p=0.01). However, low-grade UC and papillary urothelial neoplasm of low malignant potential exhibited moderate GATA3 expression. GATA3 demonstrated potential for distinguishing UC from other histological types. GATA3 expression correlates with high-grade urothelial cancer and invasive behavior, suggesting its utility as a diagnostic marker in challenging cases.

Diagnostic and Prognostic Roles of GATA3 Immunohistochemistry in Urothelial Carcinoma.

This study aimed to evaluate the diagnostic and prognostic roles of GATA-binding protein 3 (GATA3) immunohistochemistry in urothelial carcinoma (UC) using a meta-analysis. We investigated GATA3 immunohistochemical expression rates and performed a subgroup analysis based on tumor site, study location, and histological subtypes. The overall survival rates of patients with GATA3-positive and -negative UC were compared. The estimated GATA3 expression rate was 0.748 (95% confidence interval [CI]: 0.704-0.787). GATA3 expression rates in the urinary bladder and urinary tract were 0.775 (95% CI: 0.727-0.818) and 0.614 (95% CI: 0.426-0.774), respectively. The GATA3 expression rates of noninvasive and invasive UCs were 0.965 (95% CI: 0.938-0.980) and 0.644 (95% CI: 0.581-0.702), respectively. In invasive UCs, there was a significant difference in GATA3 expression between non-muscular invasion and muscular invasion subgroups (0.937, 95% CI: 0.883-0.967 vs. 0.753, 95% CI: 0.645-0.836). GATA3 expression was the highest in the microcytic subtype among the histologic subtypes (0.952, 95% CI: 0.724-0.993). There was a significant correlation between GATA3 expression and better prognosis (hazard ratio: 0.402, 95% CI: 0.311-0.521). Taken together, GATA3 expression significantly correlated with low-stage and better prognosis in UC. GATA3 expression is highly variable across histological subtypes, and one should be careful while interpreting GATA3 expression.

Comprehensive Immunohistochemical Analysis of Mesonephric Marker Expression in Low-grade Endometrial Endometrioid Carcinoma.

Immunohistochemical markers shown to be useful in identifying/confirming mesonephric/mesonephric-like differentiation (MLD markers) include thyroid transcription factor (TTF1), GATA-binding protein 3 (GATA3), and cluster of differentiation 10 (CD10). Only a few studies have examined the expression levels of MLD markers in endometrial endometrioid carcinomas (EECs). This study aimed to analyze the frequency and pattern of MLD marker expression in low-grade EECs. We performed immunostaining for the detection of TTF1, GATA3, and CD10 expression in 50 low-grade EEC tissue samples and evaluated their staining proportion and intensity. Nine tumors (18.0%) expressed at least one MLD marker in varying proportions and intensities, and 2 of these tumors were positive for 2 MLD markers (TTF1/GATA3 and GATA3/CD10, respectively). Three (6.0%) tumors showed moderate-to-strong nuclear TTF1 immunoreactivity in ≤5% of the tumor cells. Five tumors (10.0%) had at least moderate nuclear GATA3 staining, and three of them displayed a staining proportion of ≥15%. Three tumors (6.0%) were focal (mean proportion, 15%) but strongly positive for CD10. Our findings indicate that a subset of EEC can express one or more MLD markers with varying staining proportions and intensities. Given that a diagnosis of uterine mesonephric-like adenocarcinoma should be established based on a combination of characteristic histologic features, unique immunophenotypes, and confirmed molecular findings, pathologists should not exclude EEC based only on the presence of focal immunoreactivity for MLD markers. Awareness of the atypical expression patterns of MLD markers in EEC helps pathologists avoid misdiagnosing EEC as a uterine mesonephric-like adenocarcinoma.

Crocin Inhibits the Type 2 Inflammatory Response Produced by ILC2s in Eosinophilic Nasal Polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is subdivided into type 1 and type 2 inflammatory responses according to the mucosal inflammatory patterns. Crocin can reduce the level of T-helper type 2 cell (Th2) cytokines, such as interleukin-4 (IL-4), and inhibit the nuclear factor kappa-B (NF-κB) signaling pathway. This study aimed to investigate the role of group 2 innate lymphoid cells (ILC2s) in type 2 inflammation in eosinophilic nasal polyps and the inhibitory effect of crocin on this inflammation. Immunohistochemistry and immunofluorescence were used to detect the expression of transcription factors and the infiltration of ILC2s in tissues. An ILC2 stimulation model in vitro was constructed based on IL-33 stimulation and treated with crocin. The explant models were constructed and treated with crocin to detect the expression of type 2 inflammation-related factors. Significantly more GATA-binding protein-3 (GATA3)-positive cells and chemoattractant receptor-homologous molecule expressed on T-helper type 2 cell (CRTH2)-positive cells, but fewer T-box expressed in T cell (T-bet)-positive cells, were found in eosinophilic nasal polyps (NPwEos). The expression levels of GATA3 and CRTH2 were significantly higher in NPwEos. Recombinant IL-33 stimulation increased the expression of GATA3, CRTH2, and type 2 cytokines (IL-4, IL-5, and IL-13) in ILC2s. In an IL-33-stimulated in vitro ILC2 culture model, crocin inhibited the type 2 inflammatory response, especially at lower concentrations (10 µM). The explant organoids of NPwEos were constructed in vitro, and Staphylococcus aureus enterotoxin B (SEB) was used to construct the type 2 inflammation model. Crocin at 10 µM concentration inhibited type 2 inflammation induced by SEB-stimulated explants. Crocin inhibited type 2 inflammation induced by ILC2 activation at low concentrations via inhibiting the activation of NF-κB.

Eugenol Essential Oil and Nanoemulsion as Antihydatic Agents with Antifibrotic and Immunomodulatory Effects in Cystic Echinococcosis.

Conventional scolicidal agents are still unsatisfactory in combating hydatid disease due to their low efficacy and increased drug side effects. Therefore, novel scolicides are required. This study aimed to evaluate the antihydatic and immunomodulatory effects of eugenol essential oil (Eug) and its nanoemulsion (Eug-NE) in cystic echinococcosis (CE). Eug and Eug-NE were administered orally to CE-infected rats and compared to albendazole (ABZ). Hydatid cyst development was assessed based on organ weight and hypertrophy indicators of the infected organs, along with a histopathological and histochemical evaluation of collagen content. The immunomodulatory effects of treatment on CE were evaluated by serum cytokine levels measurement of interferon-γ (IFN-γ) and interleukin (IL)-4 and immunohistochemical (IHC) analysis of signal transducer and activator of transcription 4 (STAT4) and GATA-binding protein 3 (GATA3) markers. Eug-NE was the most effective in reducing the cyst weights, organ weights, and hypertrophy indicators and improving histopathological lesions with reduced collagen content. Eug and Eug-NE significantly increased the IFN-γ levels and decreased the IL-4 levels, while IHC analysis demonstrated a significant reduction in STAT4 and GATA3 expression in all treated groups. Eug and Eug-NE demonstrated antihydatic and preventative effects, with a substantial decrease in liver fibrosis compared to that of ABZ. Besides their promising immunomodulatory effects, their good treatment response suggests their use as alternatives or complementary scolicidal agents in hydatid cyst treatment.

GATA Binding Protein 3 (GATA-3) expression evaluation as prognostic factor in breast cancer and its relationship with other immunemarkers.

Breast cancer is the most frequent cancer in which the mortality rate could be decreased by proper management. The GATA3 transcription factor is one of the most frequently mutated genes in breast cancer. We studied the immunohistochemical (IHC) expression of estrogen and progesterone receptor, human epidermal growth factor receptor 2, and GATA-3 in 166 radical/partial mastectomy specimens having different histologic grades and stages of breast carcinoma. All samples were obtained from the pathology department of Sina hospital in Tehran-Iran from 2010 to 2016. There was a direct relationship between the luminal subtype carcinoma and higher GATA-3 expression (P-value: 0.001) and between triple-negative carcinoma and lower GATA-3 expression (P-value: 0.001). Moreover, there was a direct relationship between the metastasis rate and the tumor's grade with GATA-3 staining (P-value: 0.000 and 0.001, respectively). GATA-3 expression is related to the histopathologic and prognostic factors. GATA3 can be introduced as an important predictor in breast cancer patients.

GATA-3 expression in breast cancer is related to intratumoral M2 macrophage infiltration and tumor differentiation.

Accumulating evidence indicates that tumor-associated macrophages promote tumor progression and that high macrophage infiltration is correlated with advanced tumor stages and poor prognosis in breast cancer. GATA binding protein 3 (GATA-3) is a differentiation marker related to differentiated states in breast cancer. In this study, we explore how the extent of MI relates to GATA-3 expression, hormonal status, and the differentiation grade of breast cancer. To examine breast cancer in early development, we selected 83 patients that were treated with radical breast-conserving surgery (R0), without lymph node metastases (N0) or distant metastases (M0), with and without postoperative radiotherapy. Immunostaining of M2-macrophage-specific antigen CD163 was used to detect tumor-associated macrophages, and macrophage infiltration was estimated semi-quantitatively into no/low, moderate, and high infiltration. The macrophage infiltration was compared to GATA-3, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), and Ki-67 expression in cancer cells. GATA-3 expression is associated with ER and PR expression but inversely correlated to macrophage infiltration and Nottingham histologic grade. High macrophage infiltration in advanced tumor grade was associated with low GATA-3 expression. The disease-free survival is inversely related to Nottingham histologic grade in patients having tumors with no/low macrophage infiltration, a difference that is not found in patients with moderate/high macrophage infiltration. These findings indicate that macrophage infiltration might impact the differentiation, malignant behavior, and prognosis of breast cancer, regardless of the morphological and hormonal states of the cancer cells in the primary tumor.

The Value of Immunohistochemical Expression of TOX, ICOS, and GATA-3 in the Diagnosis of Mycosis Fungoides.

Mycosis fungoides (MF) is considered the commonest type of cutaneous T-cell lymphoma representing about 50% of all primary cutaneous lymphomas. Differentiation between MF and another inflammatory dermatitis (BIDs) is important to ensure proper management. We aimed to evaluate the immunohistochemical expression of T OX, ICOS, and GATA binding protein 3 (GATA-3) in early stages MF (stage IA and IB) to establish their diagnostic value and to guide the use of inhibitors in the treatment of cutaneous T-cell lymphomas. A retrospective study of 75 skin paraffin blocks (punch biopsy) 40 cases of MF and 35 cases of eczematous dermatitis as a group representing other inflammatory dermatitis were retrieved from archives of the pathology department of our University, during the period from October 2017 to May 2021. About 98% and 90% of patients in the MF group had positive T OX and ICOS, while 70% of them had positive GATA-3. High expression of T OX, ICOS, and GATA-3 was associated with higher stages. T OX is considered a diagnostic marker for early MF. The importance of identifying novel markers in MF expressed by immunohistochemistry, such as ICOS, has been established. According to our results, GATA-3 could be used as an accessory marker in the diagnosis of MF when combined with T OX and ICOS in a panel.

Nucleus Pulposus Cells from Calcified Discs Promote the Degradation of the Extracellular Matrix through Upregulation of the GATA3 Expression.

Disc calcification is strongly associated with disc degeneration; however, the underlying mechanisms driving its pathogenesis are poorly understood. This study aimed to provide a gene expression profile of nucleus pulposus cells (NPCs) from calcified discs, and clarify the potential mechanism in disc degeneration. Primary NPCs were isolated from calcified and control discs (CAL-NPC and CON-NPC), respectively. The proliferation and extracellular matrix (ECM) metabolism capacities of the cells were evaluated using MTT and Western blotting, respectively. RNA sequencing was used to identify differentially expressed genes (DEGs) in the CAL-NPCs. The biological functions of the DEGs were analyzed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. The transcription factor database and Cytoscape software were used to construct the transcription factor-DEGs regulatory network. The role of the verified transcription factor in NPC proliferation and ECM metabolism was also investigated. The CAL-NPCs exhibited a lower proliferation rate and higher ECM degradation capacity than the CON-NPCs. In total, 375 DEGs were identified in the CAL-NPCs. The GO and KEGG analyses showed that the DEGs were primarily involved in the regulation of ribonuclease activity and NF-kappa B and p53 signaling pathways. GATA-binding protein 3 (GATA3) with the highest verified levels was selected for further studies. Overexpression of GATA3 in the CON-NPCs significantly inhibited their proliferation and promoted their ECM degradation function, while the knockdown of GATA3 in the CAL-NPCs resulted in the opposite phenotypes. This study provided a comprehensive gene expression profile of the NPCs from the calcified discs and supported that GATA3 could be a potential target for reversing calcification-associated disc degeneration.

GATA3 Encapsulated by Tumor-Associated Macrophage-Derived Extracellular Vesicles Promotes Immune Escape and Chemotherapy Resistance of Ovarian Cancer Cells by Upregulating the CD24/Siglec-10 Axis.

Tumor-associated macrophages (TAMs) possess great potential in the development of ovarian cancer (OC). Aberrant GATA-binding protein-3 (GATA3) expression has been found in TAM-derived extracellular vesicles (EVs). This study is intended to investigate the regulatory mechanism of TAM-derived EVs, expressing GATA3 in immune escape and chemotherapy resistance of OC cells. In silico analysis was employed to identify differentially expressed genes. The expression of GATA3, CD24, and sialic acid-binding igg-like lectin 10 (Siglec-10) in OC tissues and cells was characterized, with their correlation verified. OC cells were co-cultured with TAM-derived EVs and CD8+T cells. The functional significance of GATA3/CD24/Siglec-10 in immune escape and chemotherapy resistance of OC cells was assayed by the gain and loss of function experiments. In vivo experiments were also performed for further validation. High expressions of GATA3, CD24, and Siglec-10 were observed in OC tissues and cells. GATA3 could be transferred by TAM-derived EVs into OC cells, which facilitated immune escape and resistance to cisplatin of OC cells. GATA3 up-regulated CD24 to increase Siglec-10 expression. The in vivo assay confirmed the promoting effect of GATA3 delivered by TAM-derived EVs on OC through activation of the CD24/Siglec-10 axis. Collectively, TAM-derived EVs harboring GATA3 played a tumor-promoting role in immune escape and chemotherapy resistance of OC cells via the CD24/Siglec-10 axis.

Intestinal Microflora Altered by Vancomycin Exposure in Early Life Up-regulates Type 2 Innate Lymphocyte and Aggravates Airway Inflammation in Asthmatic Mice.

Allergic asthma is a chronic inflammatory disease primarily mediated by Th2 immune mechanisms. Exposure to antibiotics during early life is associated with an increased risk of allergic asthma, although the exact mechanism is not fully understood. In this study, mice were randomly divided into a normal saline control group (NS group), an OVA-induced asthma group (OVA group), a vancomycin treatment control group (VAN.NS group), and a vancomycin treatment the OVA-induced asthma group (VAN.OVA group). The results showed that vancomycin altered dominant species in experimental mice. The phylum level histogram showed that Bacteroides abundance was increased, and Firmicutes abundance was decreased in the OVA group. Airway inflammation and airway hyperresponsiveness (AHR) were aggravated in the vancomycin-exposed group. Enzyme-linked immunosorbent assay (ELISA) showed that the serum levels of IL-5, IL-13, and IL-33 in the OVA group were higher than those in the NS group, especially in the VAN.OVA group. The expression of GATA binding protein-3(GATA3) and retinoid acid receptor-related orphan receptor alpha (RORa) increased in the OVA group, even more so in the VAN.OVA group. Group 2 innate lymphoid cells (ILC2s) in the lung detected by flow cytometry was increased in OVA mice more than those in control mice, with a more remarkable increase in the VAN.OVA. Our results demonstrated that vancomycin used in early life could alter the intestinal microecology of mice, which, in turn, aggravates airway inflammation and upregulate type 2 innate lymphocytes.

Utility of TRPS-1 immunohistochemistry in diagnosis of metastatic breast carcinoma in cytology specimens

At present, GATA binding protein 3 (GATA-3) is the most frequently used diagnostic immunohistochemical (IHC) marker for breast carcinoma (BC). However, it is not specific and has very low sensitivity for triple-negative BC (TNBC). SRY-box transcription factor 10 (SOX-10) and trichorhinophalangeal syndrome type 1 (TRPS-1) have been suggested for inclusion in the diagnostic workup of TNBC. TRPS-1 has not been established in cytology specimens as a diagnostic IHC marker for metastatic BC (MBC). Hence, in the present study we evaluated the utility of TRPS-1 in diagnosing MBC in cytology specimens. MBC cases diagnosed on cytology specimens from January to October 2020 were included in the present study. Only cases with hormonal status available and ≥20 tumor cells on cell blocks were included in the study. The cell blocks were assessed for TRPS-1, GATA-3, and SOX-10 IHC marker positivity (intensity and percentage of tumor cells). The results were correlated with the specimen type (fine needle aspiration [FNA] versus body fluid) and various BC prognostic subgroups. We analyzed 61 cases, including 33 body fluid and 28 FNA (13 lymph node, 10 bone, 2 liver, 2 soft tissue, and 1 lung) specimens. TRPS-1 had 97.2% positivity in ER/PR+ (estrogen receptor/progesterone receptor-positive) MBC compared with GATA-3, which had 100% positivity in the same group. TRPS-1 showed high positivity in 35 of 37 cases (94.6%) and intermediate positivity in 1 (2.6%) and was negative/low positive in 1 case (2.7%). In contrast, GATA-3 showed high positivity for all 37 cases (100%). SOX-10 showed positivity in only 1 of 37 cases (2.7%), with intermediate positivity. In the HER2+ (human epidermal growth factor receptor 2-positive) group, TRPS-1 showed high positivity in 5 of 7 cases (71.4%), intermediate positivity in 1 case (14.3%), and negativity in 1 case (14.3%). However, GATA-3 showed high positivity in 6 of 7 cases (85.7%) and negative/low positivity in 1 case (14.3%). SOX-10 was negative in all 7 cases. In TNBC, TRPS-1 showed high positivity in 16 of 17 cases (94%) and intermediate positivity in 1(5.9%), and GATA-3 showed high positivity in 9 (53%), intermediate positivity in 2 (11.8%), and low positive/negative in 6 of the 17 cases (35.3%). TRPS-1 expression was significantly higher than GATA-3 expression for the number of positive cases (P = 0.07), mean percentage of positive tumor cells (P=0.005), and intensity of reactivity (P = 0.005). SOX-10 expression was present in only 5 of 17 cases (29%), with a mean percentage of positivity in the tumor cells of 26.5% and intensity of 0.8. No differences were found in the IHC results between the different specimen types (FNA versus fluid) in any group. TRPS-1 is a highly sensitive new diagnostic IHC marker for breast carcinoma, with a similar positivity rate in ER/PR+ and HER2+ BC compared with GATA-3 and a higher positivity rate than GATA-3 and SOX-10 in TNBC in cytology specimens. In particular, when only a few clusters of tumor cells are present on the cell block, TRPS-1 can be highly useful, because its mean percentage of positive tumor cells and intensity are higher than those of other IHC markers.

Comparison of the expression of GATA-3 protein from the transcription factor family and pathological prognostic parameters in invasive ductal carcinomas of the breast

Background GATA binding protein 3 (GATA-3) is one of the six transcription factor family members and is important for glandular development in the breast. Its expression becomes important in breast cancer. We aimed to compare GATA-3 immunoreactivity and pathological prognostic factors in patients with invasive ductal carcinoma.&#x0D; Material and Methods Our study was conducted retrospectively with 300 breast invasive ductal carcinoma patients who were operated on in our hospital between May 2013 and June 2014. Patient reports, slides and blocks in the pathology archive were scanned. GATA-3 immunohistochemical (IHC) staining was evaluated according to the nuclear staining, intensity and percentage. The relationship between clinicopathological prognostic parameters and GATA-3 IHC staining results was investigated. &#x0D; Results A positive staining was observed in 286 (95.3%) cases. According to the GATA-3 staining intensity and percentage, 210 (70%) cases stained strongly and 246 (82%) stained +4, respectively. There was a significant relationship between GATA-3 immunoreactivity with ER, PR, Cerb-B2, Ki-67, mitotic degree, mitotic count and histological grade.&#x0D; Conclusions There was a correlation between the high expression of GATA-3 and good prognostic markers. Hormone receptors can be evaluated with Cerb-B2 and Ki-67 and used as prognosis determinants in breast cancers. They can be used to identify both primary and secondary breast tumors.

Long non-coding RNA MALAT1 promotes Th2 differentiation by regulating microRNA-135b-5p/GATA-3 axis in children with allergic rhinitis.

Allergic rhinitis (AR) threatens patient survival. CD4+ T cells play key roles in AR progression. Long non-coding RNAs (lncRNAs) are key regulators of cell differentiation. Therefore, we investigated the molecular mechanism of the lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in AR. Expression levels of MALAT1, microRNA (miR)-135b-5p, interleukin-4 (IL-4), and GATA-binding protein 3 (GATA-3) in the nasal mucosa of AR patients were quantified. CD4+ T cells were isolated from the peripheral blood of healthy volunteers and treated with ovalbumin (OVA) and Th2 inducers. After MALAT1 and miR-135b-5p levels changed in CD4+ T cells, the proportion of IL-4-expressing cells and the levels of IL-4 and GATA-3 in OVA-induced CD4+ T cells were determined. Binding relationships among MALAT1, miR-135b-5p, and GATA-3 were predicted and verified. Rescue experiments were performed to confirm the role of the MALAT1/miR-135b-5p/GATA-3 axis in Th2 differentiation of CD4+ T cells. MALAT1, IL-4, and GATA-3 expression was upregulated, whereas miR-135b-5p expression was downregulated, in patients with AR. MALAT1 knockdown or miR-135b-5p overexpression in CD4+ T cells notably decreased the proportion of IL-4-expressing cells and downregulated GATA-3 and IL-4 expression in OVA-induced CD4+ T cells. MALAT1 and GATA-3 exhibited competitive binding toward miR-135b-5p. MALAT1 facilitated CD4+ T cell Th2 differentiation via the miR-135b-5p/GATA-3 axis. MALAT1 facilitated AR development by facilitating CD4+ T cell Th2 differentiation via the miR-135b-5p/GATA-3 axis. This study may provide guidance for clinical treatment of AR.

In Vitro and In Vivo Validation of GATA-3 Suppression for Induction of Adipogenesis and Improving Insulin Sensitivity.

Impaired adipogenesis is associated with the development of insulin resistance and an increased risk of type 2 diabetes (T2D). GATA Binding Protein 3 (GATA3) is implicated in impaired adipogenesis and the onset of insulin resistance. Therefore, we hypothesize that inhibition of GATA3 could promote adipogenesis, restore healthy fat distribution, and enhance insulin signaling. Primary human preadipocytes were treated with GATA3 inhibitor (DNAzyme hgd40). Cell proliferation, adipogenic capacity, gene expression, and insulin signaling were measured following well-established protocols. BALB/c mice were treated with DNAzyme hgd40 over a period of 2 weeks. Liposomes loaded with DNAzyme hgd40, pioglitazone (positive), or vehicle (negative) controls were administered subcutaneously every 2 days at the right thigh. At the end of the study, adipose tissues were collected and weighed from the site of injection, the opposite side, and the omental depot. Antioxidant enzyme (superoxide dismutase and catalase) activities were assessed in animals’ sera, and gene expression was measured using well-established protocols. In vitro GATA3 inhibition induced the adipogenesis of primary human preadipocytes and enhanced insulin signaling through the reduced expression of p70S6K. In vivo GATA3 inhibition promoted adipogenesis at the site of injection and reduced MCP-1 expression. GATA3 inhibition also reduced omental tissue size and PPARγ expression. These findings suggest that modulating GATA3 expression offers a potential therapeutic benefit by correcting impaired adipogenesis, promoting healthy fat distribution, improving insulin sensitivity, and potentially lowering the risk of T2D.