Serum Β-catenin Research Articles

Role of Circ-ITCH Gene Polymorphisms and Its Expression in Breast Cancer Susceptibility and Prognosis

Introduction/Objective: Breast cancer (BC) is the first leading cause of cancer-related mortality in females worldwide. We have investigated the correlation between circ-ITCH gene polymorphisms, circ-ITCH expression, and their effect on β-catenin levels and BC development. Methods: Participants included 62 BC and 62 controls matched in terms of age. The circ-ITCH polymorphisms rs10485505 and rs4911154 were genotyped using whole blood samples. In addition, mRNA expression analysis of circ-ITCH was performed on BC tissues. The β-catenin levels in serum samples were measured using ELISA. Results: The qRT-PCR results demonstrated that circ-ITCH was significantly downregulated in BC compared to normal healthy tissues. The genotype distribution of rs10485505 and rs4911154 were significantly associated with BC risk. For rs10485505, genotype CT and TT were significantly associated with an increased BC risk. In contrast, there was a significant association between rs4911154, genotypes GA and AA, and an increased BC risk. Regarding the rs10485505 genotype, carriers of the T allele frequently have a poor prognosis compared to carriers of the CC genotype. Serum β-catenin in the BC patients’ group was significantly higher than in the control group. The relative expression levels of circ-ITCH were remarkably decreased in the BC samples of patients carrying the A allele at rs4911154 compared to patients with a GG genotype. Conversely, β-catenin protein levels were increased in patients carrying the A allele, while rs10485505 genotype carriers of the CT and TT genotypes showed downregulation of circ-ITCH expression fold compared to the CC genotype. Contrarily, β-catenin levels markedly increased in TT and CT genotypes compared with the CC genotype. Conclusions: Our research showed that the rs10485505 polymorphism (T allele) and the rs4911154 polymorphism (A allele) are associated with the risk and prognosis of BC. This finding may be due to the effect on the level of circ-ITCH mRNA expression in BC tissues as well as the level of β-catenin in BC patients.

Serum β-catenin changes vary among different stages of osteonecrosis of the femoral head: an exploratory biomarker study

BackgroundWnt/β-catenin signaling pathway is closely related to the pathogenesis Osteonecrosis of the femoral head (ONFH). β-catenin, as a major component of Wnt signaling pathway, plays a vital role in the proliferation of osteoblasts. But the effect of altering β-catenin level on the early diagnosis and staging of ONFH has not been studied. Our purpose is to investigate the role of β-catenin level in the progress of ONFH.MethodOne hundred and one patients with three stages of ONFH and fifty healthy controls were recruited between May 2016 and November 2016. We divided the patients into 32 cases of stage II, 41 cases of stage III and 28 cases of stage IV according to the Association Research Circulation Osseous (ARCO) classification. We evaluated the clinical bone histomorphology, expression position and level of β-catenin as well as the plasma β-catenin level. We investigated the level of β-catenin from the serum and tissue samples using ELISA and Western Blot assay. We also evaluated the expression of β-catenin in bone tissue by immunohistochemistry. Data were analyzed by independent t-test and ANOVA.ResultsWe found that the mean (± SD) serum level of β-catenin was 66.99 ± 3.032 ng/ml in the ONFH patients, which was higher than 20.14 ± 1.715 ng/ml observed in the control group (P < 0.001). Moreover, the β-catenin levels were 49.30 ± 4.649 ng/ml, 72.54 ± 4.864 ng/ml and 79.10 ± 4.773 ng/ml in the ONFH patients with ARCO stage II, stage III and stage IV respectively, showing significant difference among them (P < 0.001). We also found that the area under the curve (AUC) calculated by ROC curve analysis to determine the values for β-catenin levels in ONFH compared with those in the control group was 0.9358 (P < 0.001), where the sensitivity was 77.23% and specificity was 98.00%.ConclusionOur results indicate that the increased β-catenin may play a vital role in the progress of ONFH and the level of β-catenin is correlated with ARCO stages. The cut-off concentration may be used as one of the sensitive marks to assess the disease process of ONFH.

Wnt10a missense gene polymorphism association with obesity risk: List of literature and a case-control study with Roc analysis for serum β-catenin level in Egypt

BackgroundGenome-wide association studies have been implicated in the pathogenesis of several diseases including obesity. Few Recent studies reported wnt10a protein as a negative regulator for the adipogenesis process. However, to our knowledge, no studies discussed the role of SNP in the mechanism through which wnt10a gene mediate its role in adipogenesis suppression. Objectiveswe intended to investigate the association between missense and non-sense pathogenic polymorphisms of wnt10a gene and obesity risk in the Egyptian population. In addition, we aimed to determine the diagnostic accuracy of serum β-catenin level, an important modulator of Wnt/β-catenin signaling in the obesity pathogenesis. It is worth noting, that it is the first study to discuss wnt10a gene polymorphisms and serum β-catenin level with obesity risk. MethodsOur study included 96 obese and 102 non-obese of unrelated Egyptian volunteers. All the subjects underwent measurement the level of serum fasting glucose level, lipid profile, serum β-catenin, and CBC. RFLP-PCR method was used to genotype both wnt10a gene polymorphisms (rs121908119-rs141074983). ResultsOur results showed that missense polymorphism of arginine to cysteine (rs141074983) SNP may be associated with obesity risk under different genetic models. The minor allele carrier (CT and TT) was highly associated with obesity (OR = 3.7 (1.3–7.07), p = 0.006). In contrast, the decrease in serum β-catenin level in obese than non-obese volunteers lacked the required statistical confidence (p > 0.05). ConclusionThe substitution of arginine to cysteine (rs141074983) in wnt10a gene is strongly associated with increased risk for obesity in the Egyptian population and larger studies can confirm our results.

The WNT/β-catenin signalling pathway induces chondrocyte apoptosis in the cartilage injury caused by T-2 toxin in rats

We investigated whether the WNT/β-catenin signalling pathway is involved in paediatric Kashin–Beck disease (KBD) and T-2-toxin-induced cartilage injury in rats to better understand the mechanism of KBD. One hundred twenty-two children were selected and assigned to the case (31), internal control (41), and external control (50) groups. The serum β-catenin and bone morphogenetic protein 2（BMP2）levels in each group were measured and compared. Thirty-six rats were randomly assigned to three groups, which received no intervention, T-2 toxin, or solvent. After 18 weeks, the expression of LDL receptor related proteins 5 (LRP5), β-catenin, BMP2, BAX, BCL2, APAF1, and caspase 9 was measured and compared. The serum BMP2 levels were significantly elevated in the children with KBD and in the rats treated with T-2 toxin. In the T-2 toxin group, LRP5 and β-catenin expression was reduced, whereas BAX, APAF1, and caspase 9 expression was increased. In conclusion, the WNT/β-catenin signalling pathway is suppressed in KBD, which induces chondrocyte apoptosis, leading to cartilage injury. Therefore, BMP2 may play a role in the pathogenesis of KBD.

ROLE OF GSK-3 IN Wnt/β-CATENIN SIGNALING PATHWAY IN OBESITY

The complexity of the adipogenesis mechanism results from the impact of multiple cues, among which an important place is held by the components of the Wnt signaling pathway. The search for potential markers of the development of diseases related to obesity aroused an interest in the study of GSK-3 (glycogen synthase kinase), β-catenin. GSK-3β is an intracellular serine / threonine kinase found in the cytoplasm, nucleus, mitochondria, synthesized in all body tissues and involved in regulating metabolic processes, cell proliferation, apoptosis etc. The first of the discovered functions of GSK-3β was the regulation of glycogen synthesis. Active GSK-3β phosphorylates and thereby inhibits glycogen synthase. As a result of the insulin binding to the cell receptor via inositol-3-phosphate, protein kinase B (Akt1) is activated, which, in turn, phosphorylates and inhibits GSK-3β. In addition, GSK-3β is involved in the regulating glucose metabolism. The most important function of GSK-3β is the inhibition of the β-catenin protein. In a resting cell, GSK-3β in complex with the APC and Axin proteins binds and phosphorylates the β-catenin transcription factor, which leads to its ubiquitination and degradation. When Wnt proteins act on the cell, the Dvl protein is activated, which, by binding to GSK-3β, releases β-catenin, preventing its degradation, however, the role of GSK3α/β in the adipocyte inflammatory response has not yet been fully investigated, therefore it seems promising to study the role of GSK-3 in the Wnt/β-catenin signaling pathway in obesityThe aim of the study was to assess the activity of the components of the Wnt signaling pathway in obese patients by measuring the serum level of GSK-3 and β-catenin. There were enrolled 32 patients with progressive forms of I-III degree obesity in the absence of diabetes mellitus. The concentration of serum GSK-3α, GSK-3β, and β-catenin was measured by enzyme-linked immunoassay. Data are presented as absolute and relative (%) number of patients; arithmetic mean; medians, 1 and 3 quartiles – Ме (Q0.25-Q0.75). Obese patients contained a 7.5-fold increased serum level of GSK-3α (785 (371-1317.5) pg/ml) compared to healthy individuals 105 (102.5-110) pg/ml, (p &lt; 0.001), paralleled with increased amount of GSK-3β, which level in obese patients was 295 (190-695) pg/ml, which is by 18.3% higher than those in healthy individuals 241 (218.75-287.5) pg/ml, p = 0.111. Amount of GSK-3 depending on the degree of obesity tended to increase, most often coupled to decreased β-catenin level which is consistent with the literature data and can be considered as a prognostic criterion for the course of pathological processes in obesity.

Role of WNT signaling morphogenic proteins (sclerostin and β-catenin) in adipogenesis

Adipogenesis relies on complex and multi-faceted mechanism, as it is influenced by multiple cues, including the components from the WNT signaling pathway. The search for possible markers of developing metabolic diseases associated with obesity accounted for an interest to study the morphogenic proteins sclerostin and β-catenin. The aim of the study was to evaluate activity of the WNT signaling pathway in obese patients by measuring level of serum sclerostin and β-catenin proteins. Materials and Methods. There were enrolled 32 patients with metabolic syndrome featured with progressive forms of obesity (class I-III) lacking diabetes mellitus. Concentration of serum sclerostin and β-catenin was measured by using enzyme-linked immunosorbent assay. Data were presented as absolute and relative (%) number of patients; arithmetic mean; medians, 1 and 3 quartiles – Ме (Q0.25-Q0.75). In obese patients, serum sclerostin level (260 (230-308.75) pg/ml) was increased by 13.5% compared with healthy individuals (225 (220-230) pg/ml, (p 0.001)); concentration of serum sclerostin tended to increase depending on obesity class, most in parallel with decreased β-catenin level, being in agreement with previous studies that might be considered as a prognostic criterion for assessing course of pathological process in obesity.

Role of gene polymorphisms in obesity incidence in Egypt

Background: As Egypt's current policy is heading towards a comprehensive renaissance. Therefore, determining the risk factors of obesity, which represents the key factor for most chronic diseases and disability, is the right way to promote the health, social and economic aspects of Egyptian citizens. Wnts are secreted glycoproteins and comprise a large family of nineteen proteins in humans hinting to a daunting complexity of signaling regulation, function and biological output. Recent studies suggest that WNT10a may play a role in the negative regulation of adipocyte differentiation. Objectives: The goal of our study is to investigate the association between Wnt10A gene polymorphisms and obesity risk in Egyptian population. In addition, we aimed to determine the participation of Wnt/β-catenin signaling pathway in adipogenesis by determining the serum β-catenin level. It is worth noting, that it is the first study to discuss Wnt10A gene polymorphisms and serum β-catenin level in Egyptian population. Methods: our study included 48 obese and 48 non-obese of Egyptian volunteers. All of them are unrelated persons without any chronic disease. All the subjects underwent the same investigations, including CBC, serum glucose level , lipid profile, serum β-catenin level, and genotyping for Wnt10A gene polymorphisms (rs121908119- rs141074983) using RFLP-PCR method. Results: our results showed that (rs141074983) SNP is associated with obesity risk. There was high significant difference between obese and non-obese volunteers under codominant, dominant, heterozygote, and allelic models (P 0.05). Similarly, the decrease in serum β-catenin level in obese than non-obese volunteers lacked the required statistical confidence (p>0.05). Conclusion: The Wnt10a SNP (rs141074983) is strongly associated with increased risk for obesity in Egyptian population and larger studies can confirm our results.

Serum Expression of β-Catenin Is a Potential Detection Marker in Patients with Colorectal Cancer.

Object To investigate the correlation between the level of serum β-catenin and the disease progression of colorectal polyp (CRP) and colorectal cancer (CRC) and find its potential diagnostic value. Methods A total of 327 clinical serum samples and their electronic medical records were collected. Detecting by enzyme-linked immunosorbent assay (ELISA), the correlations of serum β-catenin with tumor marker carcinoembryonic antigen (CEA) and CRC clinicopathological parameters and the receiver operating characteristic (ROC) curve were analyzed. Results Serum β-catenin levels in the CRP and CRC patients were significantly higher than those in the healthy control (HC) group (P < 0.05 and P < 0.001). Compared with CRP, serum β-catenin level in CRC was also increased (P < 0.05). However, there was no significant difference in gender, age, location, tumor size, Dukes staging, or metastasis (P > 0.05) between serum β-catenin and clinical parameters of CRC. There was no correlation between serum β-catenin levels and CEA in CRC patients (P = 0.14). ROC curve analysis showed that serum β-catenin possessed the maximum diagnostic efficiency in CRP (AUC = 0.73, P < 0.05) with 86.41% sensitivity and 51.56% specificity. β-Catenin combined with CEA had the highest diagnostic efficiency (AUC = 0.88, P < 0.05) with 81.88% sensitivity and 73.44% specificity. With CRC patients from CRP patients, ROC analysis of the combining detection (AUC = 0.70, P < 0.05) had the 70% sensitivity and 84.5% specificity. Conclusion The serum β-catenin levels are gradually increased in CRP and CRC, while there is no correlation between its levels and CRC disease process. Single serum β-catenin or combined CEA would be one of the potential candidate biomarkers for colorectal disease diagnosis.

Clinical study on the effect of changes of expression levels of β-catenin, ferritin and alkaline phosphatase on the progression of osteoporosis

Objective To explore the effects of changes in expression levels of β-catenin, SF and ALP on the development of osteoporosis. Methods Eighty women with osteoporosis were divided into menopausal group (i.e. menopausal women, 40 cases) and reproductive age group (normal menstruation women, 40 cases). The menopausal group was further divided into A, B, C and D groups according to the time of menopause (1-5, 5-10, 10-15, 15-20 years), to explore the different stages of the occurrence and development of estrogen-related osteoporosis. Change. Bone mineral density of tibia and lumbar spine was measured by multispectral imaging system, and serum levels of β-catenin, SF and ALP were measured by enzyme-linked immunosorbent assay (ELISA). Results The tibia bone density and lumbar vertebra bone density in the menopausal group and the reproductive age group were decreased, and the differences were statistically significant (F=12.580, P<0.05). Compared with group B of menopause group A, BMD decreased more slowly (t=6.105, P<0.05). In menopausal group C and menopausal group D, BMD decreased sharply (t=5.886, P<0.05). The expression level of ng/L serum β-catenin in the reproductive age group was higher than that of the menopausal group A [(43.24±4.58) ng/L, t=6.701, P<0.05], and B [(40.34±5.08) ng/L, t=5.129, P<0.05], and C [(30.67±4.50) ng/L, t=5.773, P<0.05]. Among the three groups, the lowest was the menopause group D [(24.34±3.28) ng/L, F=16.875, P<0.05]. With the development of osteoporosis, serum β-catenin expression level decreased gradually and presented negative correlation (r=-3.256, P<0.05). The expression level of serum SF in the reproductive age group [(101.2±17.1) μg/L] was lower than that in the menopausal group [(150.3±14.5) μg/L, t=5.983, P<0.05], and in the menopausal group (165.6±15.8) μg/L (t=6.157, P<0.05), and in the menopausal group [(200.9±18.9) μg/L, t=7.551, P<0.05]. Among the three groups, D (269.7±13.1) μg/L was the highest in the menopause group (F=13.820, P<0.05). With the occurrence of osteoporosis, serum SF expression level gradually increased, showing a positive correlation (r=3.237, P<0.05). The expression level of serum ALP in the reproductive age group (0.456±0.029) was higher than that in the menopausal group (0.402±0.01, t=6.328, P<0.05), and in the menopausal group (0.389±0.034, t=5.496, P<0.05), and in the menopausal group (0.308±0.019, t=5.425, P<0.05). Among the three groups, the lowest was D (0.235±0.023) in the menopausal group (F=12.885, P<0.05). With the occurrence of osteoporosis, serum ALP expression level decreased, showing a negative correlation (t=-0.795, P<0.05). Conclusion The changes of serum levels of serum β-catenin and ALP are negatively correlated with the occurrence and development of osteoporosis, and the change of serum ferritin expression level is positively correlated with the development of osteoporosis. Key words: β-catenin; Ferritin; Alkaline phosphatase; Osteoporosis

β-Catenin Protein and Its Association with Helicobacter Pylori as A Possible Marker for Gastric Cancer

Gastric cancer is still the main health threat being the third leading cause of deaths from cancers in the world, the major risk behind this disease is that it remains asymptomatic in the early stages and in (97 %) cases it metastasizes to other organs. Gastric cancer is a multifactorial disease with Helicobacter pylori (H. pylori) being the major risk factor, however, patients with gastritis, especially atrophic gastritis and gastric ulcer have been shown to be at an increased risk for developing gastric cancer. In this research, serum β-catenin, carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) were measured in patients diagnosed with gastric cancer, gastric ulcer and gastritis and also in healthy volunteers. Infection with Helicobacter pylori (H. pylori) was diagnosed by histological test, rapid urease test (RUT) and by serological tests which included IgG and IgA antibodies. The results showed that there was a large significant increase in the levels of serum β-catenin in patients with gastric cancer compared to the control group as well as to the gastritis and gastric ulcer patients. A significant increase was also seen in gastric ulcer and gastritis patients when compared to the control group. In addition, a significant increase was seen in β-catenin serum levels in patients with gastric cancer and gastric ulcer infected with H. pylori compared to the uninfected gastric cancer and gastric ulcer patients. A non-significant change was observed in the levels of CEA and CA 19-9 in all the patients compared to the control group. The results of this study suggest that β-catenin can serve as a potential biomarker for the diagnosis of gastric cancer and that H. pylori has a significant effect on the levels of this protein.

Application of On-Line nanoLC-IT-TOF in the Identification of Serum β-Catenin Complex in Mice Scald Model

Severe burn shock remains an unresolved clinical problem with an urgent need to explore novel therapeutic treatments. Intracellular β-catenin, through interaction with other proteins, has been reported to be able to regulate the size of cutaneous wounds. Higher expression of β-catenin is associated with larger sized wounds. However, the identification of serum β-catenin complex is difficult and has been rarely reported. The exploitation of more binding partners can contribute to uncovering the exact mechanisms behind serum β-catenin mediated biological effects. Here, we describe a method that consists of immunoprecipitation, SDS-PAGE, in-gel digestion, and nanoLC coupled to LCMS-IT-TOF for the investigation of serum β-catenin complex in mice scald model. Among selected gel bands obtained from the protein gels, a total of 31 peptides were identified and sequenced with high statistical significance (p<0.01). Three proteins (alpha-2-marcoglobulin, serine protease inhibitor A3K, and serine protease inhibitor A1A) were identified and validated with high reliability and high reproducibility. It was inferred that these proteins might interact with serum β-catenin, which could affect the wound healing resulting from burn shock. Our study demonstrated that the on-line coupling of nano-LC with a LCMS-IT-TOF mass spectrometer was capable of sensitive and automated characterization of the serum β-catenin complex in mice scald model.

Serum levels of β-catenin as a potential marker for genotype 4/hepatitis C-associated hepatocellular carcinoma

The global rising incidence of hepatocellular carcinoma (HCC), which parallels the increase of hepatitis C virus (HCV) prevalence, has sparked a renewed interest in discovering additional HCC serum markers. In this study, we investigated the clinical use of serum E-cadherin, ICAM, MMP-2, VEGF, OPN and β-catenin as potential diagnostic makers for HCV/genotype 4-associated HCC. Twenty cases of healthy subjects, 11 cases with asymptomatic HCV/genotype 4 carriers (ASC), 28 chronic hepatitis (CH) cases and 32 patients with HCC were enrolled in this study. Serum levels of proteins were measured by a sandwich-enzyme-linked (ELISA) assay. The diagnostic accuracy of each candidate marker was evaluated using receiver-operating characteristic (ROC) curve analysis, reporting the area under the curve (AUC) and its 95% confidence interval (CI). We demonstrated that serum β-catenin levels were significantly elevated in patients with HCC compared to those with CH, ASC and healthy controls. Among the six studied markers, β-catenin was also found to be the only marker that can significantly discriminate between patients with HCC and those with CH; therefore, β-catenin could be considered as a potential marker for early diagnosis of HCV-associated HCC in patients infected with HCV genotype 4.