Abnormal Expression Of Β-catenin Research Articles

Association between the expression of epithelial-mesenchymal transition (EMT)-related markers and oncologic outcomes of colorectal cancer.

Epithelial-mesenchymal transition (EMT) is a key step in the development of colorectal cancer (CRC) that confers metastatic capabilities to cancer cells. The present study aimed to assess the immunohistochemical (IHC) expression and impact of EMT markers, including E-cadherin, Vimentin, β-catenin, and SMAD4, on the oncologic outcomes of CRC. This was a retrospective review of 118 CRC patients. Tissue slides were retrieved from the slide archive and five tissue microarray construction blocks were constructed. IHC for E-cadherin, Vimentin, β-catenin, and SMAD4 was done. The main outcome was the association between abnormal marker expression and overall survival (OS), and disease-free survival (DFS). Adenocarcinomas accounted for 71.2% of tumors, whereas 25.4% and 3.4% were mucinous and signet ring cell carcinomas. The rates of lymphovascular invasion and perineural invasion were 72.9% and 20.3%, respectively. There was a positive, significant correlation, and association between the four markers. Abnormal expression of E-cadherin was associated with significantly lower OS (p < 0.0001) and similar DFS (p = 0.06). Abnormal Vimentin expression was associated with a significantly higher rate of distant metastasis (p = 0.005) and significantly lower OS and DFS (p < 0.0001). Abnormal expression of β-catenin was associated with significantly lower OS (p < 0.0001) and similar DFS (p = 0.15). Abnormal expression of SMAD4 was associated with significantly lower OS and DFS (p < 0.0001). Abnormal expression of all four markers was associated with a higher disease recurrence, lower OS, and lower DFS. Abnormal expression of each marker was associated with lower OS, whereas abnormal expression of Vimentin and SMAD4 only was associated with lower DFS.

Ubiquitin B, Ubiquitin C, and β-Catenin as Promising Diagnostic and Prognostic Tools in Prostate Cancer.

Prostate cancer (PC) is a major global public health concern, imposing a significant burden on men and ranking as the second most prevalent malignancy. This study delves into the intricate world of ubiquitination processes and expression regulation, with a specific focus on understanding the roles of ubiquitin B (UBB), ubiquitin C (UBC), and β-Catenin in PC development. We thoroughly analyze the expression profiles of UBB, UBC, and β-Catenin, investigating their interactions and associations with clinical and histopathological data. These findings offer valuable insights into their potential as robust prognostic markers and their significance for patient survival. Our research uncovers the upregulation of UBB and UBC expression in PC tissues, and an even more pronounced expression in lymph node metastases, highlighting their pivotal roles in PC progression. Moreover, we identify a compelling correlation between high UBB and UBC levels and diminished overall survival in PC patients, emphasizing their clinical relevance. Additionally, we observe a significant reduction in membranous β-Catenin expression in PC tissues. Importantly, abnormal β-Catenin expression is strongly associated with shorter survival in PC patients and serves as a significant, independent prognostic factor for patient outcomes. Kaplan-Meier survival analysis indicates that patients with tumors characterized by simultaneous UBB and aberrant β-Catenin expression exhibit the poorest overall survival. These collective insights underline the clinical importance of evaluating UBB, UBC, and β-Catenin as combined prognostic markers in PC.

Expression and prognostic analysis of AEG-1, NKD-1and β-catenin in gastric cancer tissues

Objective: To investigate the expressions of AEG-1, NKD-1 and β-catenin in gastric cancer (GC), and analyze their relationship with clinicopathological features and prognosis and the correlation among the three proteins.Methods: Fifty GC tissues and 50 adjacent normal tissues of patients who underwent radical gastrectomy in the Third Affiliated Hospital of Inner Mongolia Medical University during December 2015 to June 2017 were collected. The expressions of AEG-1, NKD-1 and β-catenin were detected by immunohistochemical SP method and qRT-PCR. The relationship between positive expression and clinical features and survival time of patients was analyzed, and the correlation between the three was analyzed.Results: The positive expression rates of AEG-1 and β-catenin in gastric cancer were 74% (37/50), 60% (30/50), respectively, which was significantly higher than that of paracancer tissue (18% [9/50] and 26% [13/50]). The positive expression rate of NKD1 in gastric cancer tissues was 20% (10/50), which was significantly lower than that in adjacent tissues [88% (44/50)]; and the differences were statistically significant (p &lt; . 05). AEG-1 mRNA expression level (1.0148±0.0019) and β-catenin mRNA expression level (1.0000±0.0005) in gastric cancer tissues were significantly higher than that of AEG-1 mRNA expression level (1.0002±0.0036) and β-catenin expression level in adjacent tissues mRMA expression level (0.9984±0.0012), and the differences were statistically significant (p &lt; .05). The expression level of NKD1 mRNA in gastric cancer tissues (1.0008±0.0073) was significantly lower than that in adjacent tissues (1.0291±0.0041), and the differences were statistically significant (p &lt; .05). The positive expression of AEG-1, NKD1 and β-catenin in gastric cancer tissues was not related to age, sex or tumor size (p &gt; .05), but was related to differentiation degree, TNM stage and lymph node metastasis (p &lt; .05). In gastric cancer, there was a positive correlation between AEG-1 and β-catenin protein expression (r = .678, p &lt; .001), and a negative correlation between AEG-1 and NKD1 protein expression (r = -.323, p = .012). β-catenin expression was negatively correlated with NKD1 expression (r = -.347, p = .007). The survival time of patients with positive expression of AEG-1 and β-catenin was significantly shortened compared with those with negative expression (p &lt; .05), while the survival time of patients with positive expression of NKD1 was longer than that of patients with negative expression of NKD1 (p &lt; .05).Conclusion: The abnormal expression of AEG-1, NKD-1 and β-catenin is closely related with the occurrence, development, invasion, metastasis and prognosis of gastric cancer, which provide a therapeutic target and may become markers for prognosis evaluation.

UCHL3 inhibits ferroptosis by stabilizing β-catenin and maintains stem-like properties of hepatocellular carcinoma cells

Hepatocellular carcinoma (HCC) is the most common type of primary hepatic liver cancer. Dysregulated Wnt/β-catenin activation is closely related to the progression of cancer. Nevertheless, the mechanism that sustains the abnormal expression of β-catenin in HCC has yet to be identified. In this study, we find that UCHL3 is overexpressed in HCC tissues and correlated with β-catenin protein level. High expression of UCHL3 is associated with poor prognosis. UCHL3 knockdown markedly reduces the protein level of β-catenin in HCC cells. TOP-luciferase activity and β-catenin target genes expression are also decreased upon UCHL3 depletion. We find that the ARM domain of β-catenin is required for the interaction with UCHL3. UCHL3 increases β-catenin protein stability via removing K48-specific poly-ubiquitin chains from β-catenin protein. Furthermore, the depletion of UCHL3 induces ferroptosis and hinders the growth, invasion, and stem cell properties of HCC cells. These impacts could be restored by the overexpression of β-catenin. In addition, the UCHL3 inhibitor TCID inhibits the aggressive phenotype of HCC through the degradation of β-catenin. In general, our results indicates that UCHL3 increases the stability of β-catenin, which in turn facilitates tumorigenesis of HCC, suggesting that targeting UCHL3 may be a promising approach for the treatment of HCC.

Upregulated TC1 and downregulated Chibby were correlated with the aberrant β-catenin expression in laryngeal squamous cell carcinoma.

As an important member of Wnt/β-catenin signaling pathway, the aberrant expression of β-catenin has been implicated in many cancers. Chibby, a β-catenin binding partner, is an antagonist involved in this pathway. In contrast, thyroid cancer 1 (TC1) as an activator of this pathway can relieve the antagonistic activity of Chibby on the β-catenin-mediated transcription and is high expressed in human tumors. The objectives of this study were to examine the expression of TC1, Chibby, and β-catenin and investigate the association among them in laryngeal squamous cell carcinoma (LSCC). The expression of TC1, Chibby, β-catenin, c-Myc, Cyclin D1, and matrix metalloproteinase-7 (MMP-7) were examined by immunohistochemistry in samples from 53 LSCC patients. Compared with normal laryngeal squamous epithelium (NLSE), there were upregulated expression of TC1, downregulated expression of Chibby, and aberrant cytoplasmic expression of β-catenin in the LSCC tissues (P < .001). The high expression of TC1 was correlated with the tumor site, advanced TNM and T stage, lymphovascular invasion, and poor differentiation in LSCC tissues (P < .050). There were correlations between the aberrant expression of β-catenin and the tumor site, advanced TNM and T stage, lymphovascular invasion, perineurial invasion, and poor differentiation in LSCC tissues (P < .050). Upregulated TC1 and downregulated Chibby were correlated with aberrant expression of β-catenin (P < .001), but no correlation between them (P = .076). The percent of abnormal expression of β-catenin in LSCC was 96.00% in TC1+/Chibby-, 73.68% in TC1+/Chibby+, 0.00% in TC1-/Chibby-, and 0.00% in TC1-/Chibby + group (P < .001). High expression of c-Myc, Cyclin D1, and MMP-7 was observed in LSCC tissues (P < .001). There was statistically significant about the expression of Cyclin D1 and MMP-7 among the groups of TC1+/Chibby-, TC1+/Chibby+, TC1-/Chibby-, and TC1-/Chibby + (P < .001), but was not significance about the expression of c-Myc among them (P = .339). No association was found between overall survival and the expression of TC1, Chibby, and β-catenin (P > .05). The upregulated expression of TC1 and downregulated expression of Chibby were correlated with the aberrant expression of β-catenin and the high expression of Cyclin D1 and MMP-7 in LSCC tissues.

Expression of CD68+ Tumor associated macrophages in relation to β-catenin in carcinoma stomach.

With no unified system for tumor associated macrophages (TAMs) density assessment, limited information is available on their relationship with β-catenin expression. To evaluate the density of CD68+ TAMs in gastric adenocarcinoma samples by immunohistochemistry and correlate it with grade, stage, invasion, and beta-catenin. Formalin fixed paraffin embedded (FFPE) blocks from gastrectomy specimens of proven gastric adenocarcinoma were prospectively and retrospectively were studied over a period of two years. Immunohistochemistry with CD68 and β-catenin was performed. TAM density was qualitatively compared in "tumor" versus "stroma" and "tumor" versus "non-tumor" regions. Quantitative CD68+ TAM density was assessed using different methods and compared. Cases were classified as high and low TAM based on the median value and correlated with histologic type, location, grade, stage and β-catenin expression pattern. Spearman's rank correlation test was used to compare the different methods of TAM density evaluation. The categorical variables were studied using Pearson's Chi-square or Fisher's exact test. CD68+ TAM density and β-catenin expression were correlated by analysis of variance. A P value ≤ 0.05 was taken as statistically significant. The CD68+ TAMs in the "tumor" versus "non-tumor" area (p = 0.34) and "tumor" versus "stroma distribution" (p = 0.81) did not show any statistical significance. All methods of TAM density were found to be comparable. High TAM group is significantly associated with lymphovascular invasion, tumor depth, lymph node metastasis, and abnormal β-catenin expression. TAMs density plays an important role in the tumor stage. Macrophages may possibly induce gastric cancer invasiveness by activating β-catenin pathway.

Adjuvant radiation therapy in early-stage endometrial cancer with abnormal beta-catenin expression is associated with improved local control

ObjectivesEmerging data suggests that abnormal (nuclear) β-catenin expression in some settings is associated with poorer outcomes. Our study aimed to verify the significance of abnormal β-catenin expression in early-stage endometrial cancer patients and determine if adjuvant radiation therapy (RT) improves local control. MethodsWe identified 213 patients with FIGO 2018 stage I-II endometrioid endometrial cancer who underwent surgery from 2009 to 2021 with β-catenin expression assessed. Vaginal, regional, and distant recurrences were analyzed using competing risk methods, and overall survival was analyzed using Kaplan-Meier. ResultsMedian follow up was 53.2 months; 6.9% experienced vaginal, 8.2% regional, and 7.4% distant recurrence. For the entire cohort, abnormal β-catenin expression was significantly associated with vaginal recurrence and remained significant on multivariate analysis (p = 0.03). There were 114 patients in the no specific molecular profile (NSMP) subgroup, and abnormal β-catenin expression was present in 46.5%. In the NSMP subgroup, abnormal β-catenin expression was associated with increased rates of vaginal recurrence (p = 0.06). Abnormal β-catenin expression in the NSMP subgroup was significant on multivariate analysis for vaginal recurrence (p = 0.04). RT significantly decreased vaginal recurrences in the entire cohort in patients with abnormal β-catenin expression (0%) versus wild type expression (17.5%; p = 0.03). In the NSMP subgroup 0% of patients who received RT versus 20.9% of patients who did not receive RT experienced a vaginal recurrence (p = 0.03). ConclusionUse of adjuvant RT for stage I-II NSMP endometrial cancer with abnormal β-catenin expression improved local control. RT should be considered in these patients to decrease risk of vaginal recurrences.

Improved Outcomes with Adjuvant Radiation Therapy in Early-Stage Endometrial Cancer with Abnormal Beta-Catenin Expression

<h3>Purpose/Objective(s)</h3> There is increasing data about the prognostic significance of molecular profiling for endometrial cancer outcomes and emerging data showing that abnormal (nuclear) β-catenin expression is associated with an increased risk of recurrence and poorer clinical outcomes. Our study aimed to determine if the addition of adjuvant radiation therapy following surgery improves local control in early-stage endometrial cancer patients with abnormal β-catenin expression. <h3>Materials/Methods</h3> We identified 217 patients with FIGO 2009 stage I and stage II endometrial cancer who underwent surgical resection from 2018 to 2021 at our institution and had molecular data available. We reviewed the β-catenin expression status and outcomes in these patients. Vaginal cuff recurrences, regional recurrences, and distant metastases were analyzed using competing risk methods, and overall survival was analyzed using Kaplan-Meier. <h3>Results</h3> The median follow up time was 22.5 months; 6.9% experienced vaginal, 8.2% regional, and 7.4% distant recurrence. Abnormal β-catenin expression was present in 36.8% of all patients (47% of grade 1-2 versus 17% of grade 3 patients (p=0.007)) and associated with no specific molecular profile subtype. Abnormal β-catenin expression was significantly associated with increased rates of vaginal cuff recurrence (<i>p</i>=0.02), was borderline associated with worse overall survival (<i>p</i>=0.07), and not significantly associated with regional recurrence or distant metastases. One third of patients received adjuvant radiation therapy, generally based on other pathologic factors, and radiation was significantly associated with decreased vaginal cuff recurrences in patients with abnormal β-catenin expression (<i>p</i>=0.01). This decreased incidence of vaginal recurrence was seen with the use of any type of radiation including brachytherapy or external beam radiation therapy. <h3>Conclusion</h3> Patients with Stage I-II endometrial cancer with abnormal β-catenin expression have increased rates of vaginal cuff recurrences, and adjuvant radiation therapy in this group significantly improved local control. Radiation therapy should be considered in patients with endometrial cancers demonstrating abnormal β-catenin expression to decrease the risk of vaginal cuff recurrences.

Nuclear β-Catenin Expression in the Context of Abnormal p53 Expression Indicates a Nonserous Histotype in Endometrial Carcinoma.

The interobserver reproducibility is poor for histotyping within the p53-abnormal molecular category of endometrial carcinomas (ECs); therefore, biomarkers that improve histologic classification are useful. β-catenin has been proposed to have prognostic significance in specific clinicopathologic and molecular contexts. The diagnostic utility for β-catenin expression patterns in determining the histotype of p53-abnormal ECs has not been well studied. We identified ECs molecularly classified as "p53-abnormal." The p53-abnormal classification was assigned when (1) no POLE exonuclease domain hotspot mutations identified, (2) mismatch-repair protein expression was retained, and (3) abnormal p53 expression (null or overexpression) was present. Morphology was re-reviewed and β-catenin immunohistochemistry was scored as abnormal (nuclear) or normal (membranous, non-nuclear). Eighty ECs were identified in the "p53-abnormal" category; 27 (33.75%) were uterine serous carcinomas, and 53 were of nonserous histotype: 28 uterine carcinosarcomas (35%), 16 endometrioid carcinomas (20%), 2 clear cell carcinomas (2.5%), and 7 high-grade EC with ambiguous morphology (8.75%). All 27 uterine serous carcinomas demonstrated membranous β-catenin staining. Of the 53 nonserous ECs, 11 (21%) showed abnormal β-catenin expression: 6 endometrioid carcinomas, 4 uterine carcinosarcoma, and 1 high-grade EC with ambiguous morphology. The specificity of abnormal β-catenin expression for nonserous EC is high (100%) but the sensitivity is low (21%) with positive and negative predictive values of 100% and 60%, respectively. Our data shows that abnormal β-catenin expression in the context of p53-abnormal EC is highly specific, but not sensitive, for nonserous ECs and may be of value as part of a panel in classifying high-grade EC, particularly to exclude uterine serous carcinoma when nuclear staining is present.

Pathological and Prognostic Characterization of Craniopharyngioma Based on the Expression of TrkA, β-Catenin, Cell Cycle Markers, and BRAF V600E Mutation.

We collected 61 craniopharyngioma (CP) specimens to investigate the expression of TrkA, β-catenin, BRAF gene mutation, and NTRK1 fusion in CP. There were 37 male and 24 female individuals with a median age of 34 years (range, 4–75 years). Histologically, there were 46 cases of adamantinomatous craniopharyngioma (ACP), 14 cases of papillary craniopharyngioma (PCP), and 1 case with a mixed adamantinomatous and papillary pattern. By immunohistochemistry, we found that moderate/high TrkA expression was detected in 47% (28/60) CP and was significantly higher in adult patients (p = 0.018). Interestingly, TrkA is more expressed in “whorled epithelium” cells in ACP, similar to the localization of abnormal β-catenin. The abnormal expression rate of β-catenin was 70% (43/61), and the medium/high cyclin D1 expression rate was 73% (44/60), both of which were significantly higher in ACP than in PCP. Of the CP, 41% (21/51) had a moderate/strong P16-positive signal; 58% (34/59) showed a high Ki-67 expression, and there was a significant correlation between high Ki-67 L.I. and high tumor recurrence (p = 0.021). NTRK1 fusion was not found in CP by fluorescence in situ hybridization (FISH). By PCR, 26% (15/58) CP showed BRAF V600E gene mutation, which mainly occurred in PCP (100%, 14/14) except one case of mixed CP. Moreover, TrkA expression was negatively correlated with Ki-67 index and positively correlated with P16 expression. There was a significantly negative correlation between BRAF V600E mutation and abnormal β-catenin expression. Our results demonstrate for the first time that TrkA expression might occur in CP, especially in adult CP patients, and suggest that cyclin D1 could be used for ACP histological classification in addition to β-catenin and BRAF V600E mutation, while Ki-67 could be used as a marker to predict CP recurrence.

Nanosized Titanium Dioxide Induced Apoptosis and Abnormal Expression of Blood-Testis Barrier Junction Proteins Through JNK Signaling Pathway in TM4 Cells.

Nanosized titanium dioxide (nano-TiO2) has been widely used in consumer products. It can cross the blood-testis barrier (BTB), and it has adverse effects on the male reproductive system. However, the specific mechanism has not been fully elucidated. The purpose of this study was to understand the role of the JNK signaling pathway in the apoptosis and abnormal expression of BTB junction proteins induced by nano-TiO2 in TM4 cells. After different concentration of nano-TiO2 treatments, the cell viability, apoptosis, mitochondrial membrane potential (Δψm), BTB junction proteins (Claudin-11, ZO-1, β-catenin), apoptosis-related proteins (Bax, Bcl-2, cleaved caspase-9, cleaved caspase-3), and phosphorylated (p)-JNK protein were examined. The results showed that cell viability, apoptosis rates, Δψm, and apoptosis-related protein levels changed in a concentration-dependent manner. Cell viability decreased significantly from 100μg/mL nano-TiO2 group. Apoptosis rates increased significantly from 150μg/mL nano-TiO2 group, and Δψm decreased significantly from 150μg/mL nano-TiO2 group. The protein levels of Bax, cleaved caspase-9, and cleaved caspase-3 increased significantly from 150μg/mL nano-TiO2 group, and the protein level of Bcl-2 decreased significantly from 100μg/mL nano-TiO2 group. The protein level of p-JNK increased significantly from 100μg/mL nano-TiO2 group. Abnormal expression of ZO-1 and β-catenin started from 150μg/mL nano-TiO2 group, and abnormal expression of Claudin-11 started from 100μg/mL nano-TiO2 group. Cells were treated with JNK inhibitor SP100625 to determine whether the changes of the above indicators in the concentration of 150μg/mL nano-TiO2 group can be reversed. We found that SP100625 at 20μM significantly reversed these effects. These results highlighted that nano-TiO2 could activate the JNK signaling pathway to induce mitochondria-mediated apoptosis and abnormal expression of BTB junction proteins in TM4 cells.

Effects of YAP1 and SFRP2 overexpression on the biological behavior of colorectal cancer cells and their molecular mechanisms.

Colorectal cancer (CRC) is one of the most common malignancies worldwide and has a high mortality rate. With the development of tumor molecular biology, more and more attention is being paid to the mechanisms of cell pathways in colorectal carcinogenesis, such as the Hippo/Yes-associated protein 1 (YAP1) and Wnt/β-catenin signaling pathways. The abnormal expression of YAP1 and β-catenin have been reported in CRC, and can lead to excessive cell proliferation, and eventually, tumor formation. Secreted frizzled-related protein 2 (SFRP2) levels have been found to be decreased in a variety of cancers, and SFRP2 is an antagonist that binds directly to Wnt signal. At present, the molecular basis of colorectal tumors is still not fully understood. In the present study, we sought to identify the molecular mechanisms underlying YAP1 and SFRP2 in the development of CRC. We constructed CRC cell lines that stably overexpressed YAP1 and SFRP2 using lentivirus packaging and cell infection. The levels of expression of the proteins were evaluated by western blot and immunofluorescence assays. Protein complex immunoprecipitation (Co-IP) was used to detect the interaction between YAP1, SFRP2, and β-catenin. The functional roles of YAP1 and SFRP2 in CRC was determined by a Cell Counting Kit-8 (CCK8) proliferation assay and flow cytometric apoptosis assay. The data of the present study showed that the overexpression of SFRP2 promoted the expression of YAP1 and β-catenin protein, and the overexpression of YAP1 promoted the expression of β-catenin protein. YAP1 overexpression promoted cell proliferation, while SFRP2 overexpression inhibited cell proliferation and promoted cell apoptosis. Our findings showed that the expression of YAP1, SFRP2, and β-catenin is correlated in CRC cells. The Hippo pathway and Wnt pathway interact with each other in the pathogenesis of CRC, and YAP1 and SFRP2 are involved in the formation and development of CRC.

MiRNA-34a-5p regulates progression of neuroblastoma via modulating the Wnt/β-catenin signaling pathway by targeting SOX4.

Neuroblastoma is an embryonal tumor of the autonomic nervous system with poor prognosis in children. In present study, we demonstrated the relationship of miRNA-34a-5p in the regulating of the Wnt/β-catenin signaling pathway by targeting SRY-related HMG-box (SOX4)Reverse transcription-quantitative PCR was used to detect the expression levels of miRNA-34a-5p and SoX4. Western blotting was performed to assess the protein expression levels of SoX4, Wnt, MMP9, Bax, and Bcl-2. The proliferation, apoptosis, migration and invasion of neuroblastoma cells were determined using MTT, flow cytometry and Transwell assays.In this study, we sought to investigate the role of miRNA-34a-5p on neuroblastoma and the possible molecular mechanism. We had performed in-vitro and in-vivo experiments to evaluate the effects of miRNA-34a-5p on neuroblastoma cell proliferation and invasion by altering its expression level via cell transfection. On the basis of our study, miRNA-34a-5p showed decreased expression levels in neuroblastoma. Subsequently, we manipulated miRNA-34a-5p expression through cell transfection and observed abnormal expression of β-catenin as well as the downstream targets of the Wnt/β-catenin pathway in neuroblastoma cells. With all these evidences, we determined that miRNA-34a-5p regulated Wnt/β-catenin pathway by targeting SOX4.In conclusion, our study demonstrates that miRNA-34a-5p can inhibit the over-activation of the Wnt/β-catenin signaling pathway via targeting SOX4 and further regulate proliferation, invasion of neuroblastoma cells.

Predictive value of β-catenin in bladder cancer: a systematic review and meta-analysis

Recently, some studies have suggested that the abnormal expression of β-catenin in bladder cancer (BC) is associated with the progression and survival of BC, but there are still some controversies. Hence, we elaborated on the relationship between β-catenin expression and BC through a systematic literature review and meta-analysis. As of March 2020, Embase, PubMed, the Cochrane Library, Science Direct/Elsevier, Medline and CNKI were used for systematic literature retrieval to investigate the correlation between β-catenin expression and BC. Meta-analysis was performed using Review Manager and Stata software. Fourteen studies were included, including 865 BC tissues and 106 controls. Combined ORs were identified with 95% confidence intervals (95% CIs) in a random- or fixed-effects model. We illustrated that there was a significant correlation between β-catenin and BC, that there was abnormally high expression of β-catenin in BC tissues compared with normal bladder tissues (P<0.05), and that the combined OR was 14.69 [5.73, 37.65]. Furthermore, the aberrant expression rates of β-catenin in high-grade and invasive bladder neoplasm tissues were greater than those in low-grade and non-muscle-invasive bladder tissues (P<0.05), and the combined ORs were 0.31 [0.23, 0.43] and 0.21 [0.15, 0.29]. Finally, we found through meta-analysis that the higher the expression level of β-catenin, the shorter was the progression-free survival (PFS) of patients with BC (P<0.05), and the combined OR was 2.74 [1.22, 6.14]. The present study suggests that the abnormal expression of β-catenin is associated with aggressive behavior and poor prognosis of BC, and β-catenin may be a molecular marker of the malignant degree and poor prognosis of BC.

Immunohistochemical evaluation of Ki-67, Cyclin D1 and β-catenin expression in the subtypes of triple negative breast cancer

Aim. To evaluate the expression levels of Ki-67 and cyclin D1 and β-catenin in the subtypes of triple negative breast cancer. Methods. The study was conducted on the surgical material from 60 patients of clinical stage 2A (T1N1M0 or T2N0M0) who were treated at the Rostov Research Institute of Oncology from 2012 to 2015. For immunohistochemistry, antibodies to estrogen and progesterone receptors, cytokeratins 5/6, Ki-67, cyclin D1, β-catenin, HER2/neu and EGFR proteins were used. Results. Triple negative breast cancer with the signs of basal epithelium was found to have a significantly higher expression level of Ki-67 compared to non-basal-like one. In some part of triple negative breast cancer samples overexpression of cyclin D1 was observed. The high level of cyclin D1 in the basal-like subtype was less common than in the subtypes without the signs of basal epithelium, but its average value was significantly higher. In triple negative cancer with cyclin D1 overexpression, the loss of β-catenin on the cell membrane and its abnormal accumulation in the cytoplasm was significantly more frequent. β-catenin translocation into the cell nucleus was observed only in basal-like triple negative cancer, and 2 times more often in case of cyclin D1 overexpression. Conclusion. In triple negative breast cancer tumors with overexpression of cyclin D1 and abnormal expression of β-catenin are observed in some cases; these biomarkers can be considered as potential therapeutic targets for this group of tumors.

Ankyrin-B dysfunction predisposes to arrhythmogenic cardiomyopathy and is amenable to therapy.

Arrhythmogenic cardiomyopathy (ACM) is an inherited arrhythmia syndrome characterized by severe structural and electrical cardiac phenotypes, including myocardial fibrofatty replacement and sudden cardiac death. Clinical management of ACM is largely palliative, owing to an absence of therapies that target its underlying pathophysiology, which stems partially from our limited insight into the condition. Following identification of deceased ACM probands possessing ANK2 rare variants and evidence of ankyrin-B loss of function on cardiac tissue analysis, an ANK2 mouse model was found to develop dramatic structural abnormalities reflective of human ACM, including biventricular dilation, reduced ejection fraction, cardiac fibrosis, and premature death. Desmosomal structure and function appeared preserved in diseased human and murine specimens in the presence of markedly abnormal β-catenin expression and patterning, leading to identification of a previously unknown interaction between ankyrin-B and β-catenin. A pharmacological activator of the WNT/β-catenin pathway, SB-216763, successfully prevented and partially reversed the murine ACM phenotypes. Our findings introduce what we believe to be a new pathway for ACM, a role of ankyrin-B in cardiac structure and signaling, a molecular link between ankyrin-B and β-catenin, and evidence for targeted activation of the WNT/β-catenin pathway as a potential treatment for this disease.

High Frequency of ERBB2 Activating Mutations in Invasive Lobular Breast Carcinoma with Pleomorphic Features.

Background: Characterisation of molecular alterations of pleomorphic lobular carcinoma (PLC), an aggressive subtype of invasive lobular carcinoma (ILC), have not been yet completely accomplished. Methods: To investigate the molecular alterations of invasive lobular carcinoma with pleomorphic features, a total of 39 tumour samples (in situ and invasive lesions and lymph node metastases) from 27 patients with nuclear grade 3 invasive lobular carcinomas were subjected to morphological, immunohistochemical and massive parallel sequencing analyses. Results: Our observations indicated that invasive lobular carcinomas with pleomorphic features were morphologically and molecularly heterogeneous. All cases showed absence or aberrant expression of E-cadherin and abnormal expression of β-catenin and p120. CDH1 (89%), PIK3CA (33%) and ERRB2 (26%) were the most common mutated genes. ERBB2 mutations preferentially affected the tyrosine-kinase activity domain, being the most frequent the targetable mutation p.L755S (57%). We also observed higher frequency of mutations in ARID1B, KMT2C, MAP3K1, TP53 and ARID1A in PLC than previously reported in classic ILC. Alterations related to progression from in situ to invasive carcinoma and/or to lymph node metastases included TP53 mutation, amplification of PIK3CA and CCND1 and loss of ARID1A expression. Conclusions: The high frequency of ERBB2 mutations observed suggests that ERBB2 mutation testing should be considered in all invasive lobular carcinomas with nuclear grade 3.

Expression and significance of secreted frizzled-related protein 1 and β-catenin in gingival tissue of patients with chronic periodontitis

This study aimed to investigate the expression and correlation of secreted frizzled-related protein 1 (SFRP1) and β-catenin in gingival tissues of patients with chronic periodontitis (CP). The role of the classical Wnt/β-catenin signaling pathway in the development of periodontitis was also explored. Twenty-eight patients with CP (CP group) were enrolled in this study. Among them, 16 cases were moderate CP, and 12 demonstrated severe CP. Twelve healthy cases comprised the controls (normal group). Gingival tissue was collected, and the probing depth, bleeding index, and clinical attachment loss were recorded. The expression levels of SFRP1 and β-catenin were detected by immunohistochemistry, and staining intensity was evaluated by double scoring method. SPSS 19.0 was used for statistical analysis. The staining strength scores of SFRP1 and β-catenin were 2.16±0.65 and 1.12±0.51 in the normal group, 3.57±0.45 and 2.36±0.49 in the CP group, 3.61±0.40 and 2.30±0.44 in the moderate CP group, and 3.52±0.52 and 2.45±0.55 in the severe CP group, respectively. The expression of SFRP1 and β-catenin in the CP group was higher than that in the normal group (P<0.01). A significant difference was noted between the normal group and the moderate and severe CP groups (P<0.01) but none between the moderate and severe CP groups (P>0.05). A positive correlation was found between the expression of SFRP1 and β-catenin (r=0.657, P<0.01). The expression levels of β-catenin and SFRP1 were related to periodontal indexes. The correlation between the expression of SFRP1 and probing depth was most significant (r=0.723, P<0.01), as well as that between β-catenin and bleeding index (r=0.697, P<0.01). Patients with CP exhibit elevated expression of SFRP1 and β-catenin in gingival tissues, and this event is related to the degree of periodontal destruction. Abnormal expression of SFRP1 and β-catenin may promote the development of periodontitis.

Research Progress of β-catenin in Chronic Myelogenous Leukemia -Review

β-catenin is an important member of Wnt signaling pathway. With more and more research on the relationship between β-catenin and cancers, it is noted that the concentration of β-catenin in cells is not only the landmark of activating the Wnt signaling pathway, but also a common phenomenon in various tumor cells. Moreover, abnormal expression of β-catenin is reported in blastic phase of CML and IM-resistant CML. Besides, β-catenin inhibitor is proved to be effective for the improvement of the IM susceptibility and the postponment of blastic phase. Here is to make a brief review about the mechanisms of β-catenin in the treatment of CML, such as classical signaling pathways as well as new genes and pathways.

Targeting LncRNA-MALAT1 suppresses the progression of osteosarcoma by altering the expression and localization of β-catenin.

Osteosarcoma (OS), which affects adolescents especially during a growth spurt, has the highest incidence of any primary malignant bone tumour, and a high rate of early metastasis leading to a very poor prognosis. In recent years, non-coding RNAs, especially long non-coding RNAs (lncRNAs) have attracted more and more attention as novel epigenetic regulators in a variety of tumours, including OS. Most recently, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was found to play an important role in OS progression by modulating the enhancers of zeste homolog 2 (EZH2). Furthermore, MALAT1 could inhibit the expression of E-cadherin and promote the expression of β-catenin, and this phenomenon might be the outcome of MALAT1-induced EZH2 activation. In this study, we investigated the vital function of MALAT1 in the progression of OS and its potential leading mechanism, altering the expression and localization of β-catenin via epigenetic transcriptional regulation by interacting with EZH2. With the help of MALAT1 silencing using small interfering RNAs (siRNAs), the loss of E-cadherin of MNNG/HOS cells was rescued, and the abnormal expression and localization of β-catenin were corrected at the same time. Overall, our research showed promising potential for new treatment strategies based on epigenetic regulation targeting MALAT1, which will not only coordinate with the patient's immune system, but also eliminate OS in conjunction with chemotherapy.