Comparison of growth performance, meat quality, and blood biochemical indexes of Yangzhou goose under different feeding patterns.

The East China region is the main market for the breeding and consumption of meat geese in China, in order to provide data reference for small and medium-sized farms and farmers to choose breeding methods and growth performance. This study selected 300 Yangzhou geese as materials and determined the number of geese in each group according to different modes. The meat quality, blood biochemical indicators, and economic benefits of 4 common feeding methods (Group I: full concentrate feeding; Group II: concentrate feeding in the first stage + 3% fat addition in the later stage; Group III: concentrate feeding + pasture supplementation; Group IV: grazing feeding + concentrate) in East China were analyzed. The results are as follows: The average daily weight gain of Yangzhou geese in Group IV at 5 to 8 wk old was the highest, with the highest feed utilization rate. The body weight at 8 wk old was significantly higher than that of the group III (P < 0.05). The total mortality rate of Group I and II remained at a relatively low level, while the mortality rates of Group III and IV exceeded 17%. The SR, FECR, and FECW of female geese in Groups II, III, and IV were significantly higher than those in Control group I (P < 0.05). Different feeding methods have little effect on the quality of goose breast muscles, while in terms of leg muscles, Group II has the highest binding force, significantly higher than Group I (P < 0.05). The rate of chest muscle loss in group III was significantly higher than that in groups I and II (P < 0.05). However, the pH of leg muscles in groups I, II and III was significantly higher than that in group IV (P < 0.05). Group II has the highest protein and collagen content, and Group I has the highest fat content. Except for the significantly higher histidine content in Groups I And II compared to those in Groups III and IV (P < 0.05), there was almost no significant difference in amino acid content among the groups (P > 0.05). There was no significant difference in ALB/GLO content among the 3 groups of Groups II to IV, but they were all significantly higher than those of Group I (P < 0.05). There was no statistically significant difference in other indicators among the groups (P > 0.05). There was no significant difference in the content of Ca, Cu, Fe, P, Zn, and other elements in the muscles between the groups (P > 0.05). This study solved the problems of slow growth, poor meat performance, and low economic benefits in meat goose breeding, providing theoretical basis and data support for meat goose breeding enterprises and farmers to choose appropriate breeding modes.

Exploration of the Associations of lncRNA Expression Patterns with Tumor Mutation Burden and Prognosis in Colon Cancer.

BACKGROUND: Tumor mutation burden (TMB) is emerging as a new biomarker to monitor the response of cancer patients to immunotherapy. Long non-coding RNAs (lncRNAs) are critical in regulating gene expression and play a significant role in cancer-associated immune responses. However, the association between lncRNA expression patterns and TMB levels and survival outcomes remains unknown in colon cancer. METHODS: In colon cancer patients from The Cancer Genome Atlas Program (TCGA), a multi-lncRNAs based classifier for predicting TMB levels was established using the least absolute shrinkage and selection operator (LASSO) method. The association between classifier index and immune-related characteristics of patients was also investigated. Quantitative polymerase chain reaction (qPCR) was used to verify the expression levels of these lncRNAs in normal and CRC cell lines. RESULTS: The multi-lncRNAs based classifier had ability to predict TMB level of patients with accuracy (AUC= 0.70), and the general applicability of this classifier was proved in the validation set (AUC= 0.71) and the pooled set (AUC= 0.70). The classifier index was related to three immune checkpoints (PD1, PD-L1, and CTLA-4), the infiltration level of immune cells, and immune response-related score (IFN-γ score, gene expression profiles (GEP) score, cytolytic activity (CYT) score and MHC score). A nomogram, which integrates classifier and some common clinical information, was able to predict the overall survival of colon cancer patients accurately. CONCLUSION: LncRNA expression patterns are associated with TMB, which may serve as a classifier to predict the TMB in colon cancer patients. The nomogram could potentially evaluate survival outcomes and provide a reference to better manage colon cancer patients.

Characterization of the fatty acid metabolism in colorectal cancer to guide clinical therapy.

Colorectal cancer (CRC) is one of the most common malignant tumors, with the second-highest mortality of all 36 cancers worldwide. The roles of fatty acid metabolism in CRC were investigated to explore potential therapeutic strategies. The data files were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses were used to construct a prognostic risk score model with fatty acid metabolism-related genes for predicting prognosis in CRC. Patients with a high-risk score had a poorer prognosis in TCGA cohort than those with a low-risk score and were confirmed in the GEO cohort. Further analysis using the "pRRophetic" R package revealed that low-risk patients were more sensitive to 5-fluorouracil. A comprehensive evaluation of the association between prognostic risk score model and tumor microenvironment (TME) characteristics showed that high-risk patients were suitable for activating a type I/II interferon (IFN) response and inflammation-promoting function. Tumor Immune Dysfunction and Exclusion (TIDE) and SubMap algorithm results also demonstrated that high-risk patients are more suitable for anti-CTLA4 immunotherapy. Therefore, the evaluation of the fatty acid metabolism pattern promotes our comprehension of TME infiltration characteristics, thus guiding effective immunotherapy regimens.

Effects of the injection compression process parameters on residual stress of plastic lenses.

Residual stress affects significantly the quality of plastic lenses. In this paper, the influence of process parameters on the residual stress of injection compression molded plastic lenses was investigated by orthogonal simulation. The results show that the effect of compression delay time on residual stress was the most significant, followed by compression distance and compression speed, which are both related to the compression process. Then, the relationship between the residual stress obtained by simulations and the optical path difference measured by the experiment was compared by single factor experiments of four key injection compression molding process parameters. The change trends were similar, which proves that the numerical simulation has the potential to predict the residual stress of plastic lenses and optimize the process parameters, so as to improve their optical quality.

Self-assembly hollow manganese Prussian white nanocapsules attenuate Tau-related neuropathology and cognitive decline.

Alzheimer's disease (AD) is a prevalent chronic neurodegenerative disease. However, to date, none of the developed drug candidates targeting at a single therapeutic target of AD have achieved success in clinical trials. Herein, we proposed a hypothesis of hollow manganese Prussian white nanocapsules (HMPWCs)-mediated attenuation of Tau-related pathology and alleviation of cognitive decline via simultaneously alleviating neuroinflammation, scavenging reactive oxygen species, and reducing hyperphosphorylated Tau proteins. The HMPWCs self-assemblied with manganese Prussian white analogue and bovine serum albumin via a novel biomimetic mineralization present good biocompatibility, variable valence states, and low oxidation-reduction potential. They own the outstanding capabilities of relieving oxidative stress, inhibiting Tau neuropathology, and counteracting neuroinflammation, which could be used to treat Tau-related AD-like neurodegeneration. Importantly, they can also attenuate the cognitive impairments of Tau-related AD-like rats without significant side effects. This research takes the advantages of catalytic chemistry, nanomedicine and specific neurodegenerative microenvironment together, providing an alternative efficient treatment strategy for Tau-related neurodegeneration diseases, such as AD, Pick's disease, frontotemporal dementia, Creutzfeldt-Jakob Disease and progressive supranuclear palsy.

The suppressive role of HYAL1 and HYAL2 in the metastasis of colorectal cancer.

BACKGROUND: Hyaluronidases (HAases), enzymes that degrade hyaluronan, have been widely investigated in cancer biology. However, whether HAases serve as tumor promoters or suppressors has been controversial in different cancers, and the exact role of HAases in colorectal cancer (CRC) has not been elucidated. METHODS: The expression levels of HYAL1, HYAL2, and HYAL3 in cancer and corresponding normal tissues from CRC patients were examined via immunohistochemistry. Then the correlation between HAases levels and pathological characteristics of CRC patients was analyzed. To verify the clinical data, HYAL1 and HYAL2 were downregulated or overexpressed in colon cancer cells LOVO and HCT116 to observe their influences on cell invasion and migration. For the mechanism study, we investigated the effects of HYAL1 and HYAL2 on the expression of matrix metalloproteases (MMPs)/tissue inhibitor of metalloproteases (TIMPs) and distribution of F-actin. RESULTS: All the three HAases were abnormally elevated in cancer tissues. Interestingly, HYAL1 and HYAL2, but not HYAL3, were negatively correlated with lymphatic metastasis and TNM stage. When HYAL1 and HYAL2 were knocked down, the invasion and migration abilities of colon cancer cells were accelerated, whereas overexpression of HYAL1 and HYAL2 had the opposite effects. In addition, colon cancer cells with HYAL1 and HYAL2 downregulation showed increased levels of MMP2 and MMP9, decreased levels of TIMP1 and TIMP2, and more intense F-actin stress fibers. CONCLUSIONS: Our study suggests that HYAL1 and HYAL2 suppress CRC metastasis through regulating MMPs/TIMPs balance and rearranging F-actin distribution, further inhibiting invasion and migration of cancer cells.

Efficient Synthesis of Glutamate Peptide-Estradiol Conjugate for Imaging Estrogen Receptor-Positive Diseases.

Molecular imaging of estrogen receptor-positive (ER+) pathway-activated system serves the basis of ER+ disease management such as cancers and endometriosis. ER+ patients have better response to endocrine therapy and survive twice as long as negative ER patients. However, tumor resistance resulting from clinical used aromatase inhibitors and antiestrogens is unpredictable. Radiolabeled ER+ ligand could quantify ER+ tissue uptake which helps to stage and restage of the cancer as well as endometriosis. The differential diagnosis of ER+ lesions by using a labeled ligand helps to select the patients for optimal response to endocrine therapy and to discontinue the treatment when resistance occurs. In addition, radiolabeled ER+ ligand serves as basis for image-guided response follow-up. Glutamate receptors are cell surface receptors which are overexpressed in inflammation and infection. Using glutamate peptide as a drug carrier helps to target intracellular genes via glutamate receptor-mediated process. Reports have shown that polyglutamate is a drug carrier that could alter drug solubility and enhance estrogen receptor-ligand binding pocket. However, polyglutamate was a blend of mixed polymer with a wide range of molecular weight. Thus, the structural confirmation and purity of the conjugates were not optimized. To overcome this problem, the efficient synthesis of glutamate peptide-estradiol (GAP-EDL) conjugate was achieved with high purity. EDL was conjugated site-specific at the first glutamate of GAP. The average cell uptake of 68Ga-GAP-EDL was 5-fold higher than the previous reported synthesis. The efficient synthesis of GAP-EDL has greatly enhanced sensitivity and specificity in cell uptake studies. In vivo PET imaging studies indicated that 68Ga-GAP-EDL could image ER (+) tumors in MCF-7 tumor-bearing mice. Therefore, GAP-EDL makes it possible to image ER-enriched endometriosis and cancer.

High expression of Ras-related protein 1A promotes an aggressive phenotype in colorectal cancer via PTEN/FOXO3/CCND1 pathway.

BACKGROUND: Colorectal cancer (CRC) is a commonly diagnosed digestive malignancy worldwide. Ras-related protein 1A (RAP1A) is a member of the Ras superfamily of small GTPases and has been recently identified as a novel oncoprotein in several human malignancies. However, its specific role in CRC remains unclear. METHOD: In this study, we firstly analyzed its expression and clinical significance in a retrospective cohort of 144 CRC patients. Then, cellular assays in vitro and in vivo were performed to clarify its biological role in CRC cells. Finally, microarray analysis was utilized to investigate the molecular mechanisms regulated by RAP1A in CRC progression. RESULTS: Firstly, RAP1A expression was abnormally higher in CRC tissues as compared with adjacent normal tissues, and significantly correlated tumor invasion. High RAP1A expression was an independent unfavourable prognostic factor for CRC patients. Combining RAP1A expression and preoperative CEA level contributed to a more accurate prognostic stratification in CRC patients. Secondly, knockdown of RAP1A dramatically inhibited the growth of CRC cells, while it was opposite for RAP1A overexpression. Finally, the microarray analysis revealed RAP1A promoted CRC growth partly through phosphatase and tensin homolog (PTEN)/forkhead box O3(FOXO3)/cyclin D1(CCND1) signaling pathway. FOXO3 overexpression could partly mimic the inhibitory effect of RAP1A knockdown in CRC growth. Moreover, FOXO3 overexpression inhibited CCND1 expression, but had no impact on RAP1A and PTEN expression. CONCLUSION: RAP1A promotes CRC development partly through PTEN/FOXO3 /CCND1 signaling pathway. It has a great potential to be an effective clinical biomarker and therapeutic target for CRC patients.

Tau-Targeted Multifunctional Nanocomposite for Combinational Therapy of Alzheimer's Disease.

Alzheimer's disease (AD) remains an incurable disease and lacks efficient diagnostic methods. Most AD treatments have focused on amyloid-ß (Aß) targeted therapy; however, it is time to consider the alternative theranostics due to accumulated findings of weak correlation between Aß deposition and cognition, as well as the failures of Phase III clinical trial on Aß targeted therapy. Recent studies have shown that the tau pathway is closely associated with clinical development of AD symptoms, which might be a potential therapeutic target. We herein construct a methylene blue (MB, a tau aggregation inhibitor) loaded nanocomposite (CeNC/IONC/MSN-T807), which not only possesses high binding affinity to hyperphosphorylated tau but also inhibits multiple key pathways of tau-associated AD pathogenesis. We demonstrate that these nanocomposites can relieve the AD symptoms by mitigating mitochondrial oxidative stress, suppressing tau hyperphosphorylation, and preventing neuronal death both in vitro and in vivo. The memory deficits of AD rats are significantly rescued upon treatment with MB loaded CeNC/IONC/MSN-T807. Our results indicate that hyperphosphorylated tau-targeted multifunctional nanocomposites could be a promising therapeutic candidate for Alzheimer's disease.

Stromal Expression of Vimentin Predicts the Clinical Outcome of Stage II Colorectal Cancer for High-Risk Patients.

BACKGROUND Increased expression of vimentin in tissue samples from patients with colorectal cancer (CRC) has been previously demonstrated, but its prognostic significance remains controversial, and the clinical significance for patients with stage II CRC is still unknown. The aim of this study was to evaluate the expression of vimentin in CRC and its potential prognostic significance. MATERIAL AND METHODS We analyzed vimentin expression in 203 CRC tissue samples from patients with stage II cancer using immunohistochemistry, and correlated the findings with clinicopathological patient features. CRC-specific survival (CSS) and disease-free survival (DFS) were analyzed using the Kaplan-Meier method. Univariate and multivariate analysis was performed using the Cox proportional hazards method for survival. RESULTS Vimentin expression was significantly correlated only with tumor (T) stage (p=0.024). Kaplan-Meier survival analysis indicated that vimentin expression could stratify the CSS and DFS of patients with stage II CRC at high risk (p=0.029, p=0.042, respectively), but not those of low-risk stage II patients (p=0.208, p=0.361, respectively). Univariate and multivariate analysis further revealed that stromal vimentin expression is an independent prognostic factor for CSS and DFS of high-risk stage II patients (p=0.043, p=0.022, respectively). Moreover, high-risk stage II patients with low stromal vimentin expression benefitted more from standard adjuvant chemotherapy than those with high stromal vimentin expression (CSS: p=0.012 vs. p=0.407; DFS: p=0.017 vs. p=0.420). CONCLUSIONS Our study suggests that stromal vimentin expression is a promising indicator for survival prediction and adjuvant chemotherapy response in patients with stage II CRC with high-risk factors for recurrence.

Up-regulation of carcinoembryonic antigen-related cell adhesion molecule 1 in gastrointestinal cancer and its clinical relevance.

Serum carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is dysregulated in various malignant tumors and has been associated with tumor progression. However, the expression and regulatory mechanisms of serum CEACAM1 in gastrointestinal cancer are still unclear. The expression ratio of the CEACAM1-L and CEACAM1-S isoforms has seldom been investigated in gastrointestinal cancer. In this study, we intended to explore the expression and diagnostic value of CEACAM1 in gastrointestinal cancer. Serum CEACAM1 levels were measured by enzyme-linked immunosorbent assay. The protein expression and distribution of CEACAM1 in tumors were examined by immunohistochemical staining. The expression patterns and ratio of CEACAM1-L/S were analyzed by reverse transcription-polymerase chain reaction. The results showed that serum CEACAM1 levels were significantly higher in cancer patients than in healthy controls. CEACAM1 was found in secreted forms within the neoplastic glands, and its expression was more intense at the tumor invasion front. The CEACAM1-L/S (L:S) ratios were up-regulated during tumorigenesis. Our data suggest that the serum level of CEACAM1 may be used to discriminate gastrointestinal cancer patients from health controls.

Anorectal functional outcome following laparoscopic low anterior resection for rectal cancer.

Low anterior resection (LAR) with total mesorectal excision has been considered a standard treatment for patients with rectal cancer. However, the functional outcome and life quality of laparoscopic LAR (LLAR) in Chinese patients remain unclear. A cohort of 51 Chinese patients (22 men and 29 women) who had undergone LLAR was included in this study. Anorectal manometry combined with the Wexner scores questionnaire were applied to assess functional outcome preoperatively (1 week) and postoperatively (at 3, 6 and 9 months). The validated Chinese versions of the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-CR38 questionnaires were also used to assess the patients' quality of life at the indicated time points. The results demonstrated that the manometric parameters exhibited a temporary decrease at 3 months postoperatively, but a gradual increase at 6 and 9 months, while the Wexner scores exhibited an opposite trend. Furthermore, patients with high anastomoses had significantly higher manometric parameters, a lower frequency of incontinence and lower Wexner scores compared with those with low anastomoses at 9 months (all P<0.05). For the entire cohort, quality of life at 3 months postoperatively was worse compared with the preoperative level, but returned to normal by 9 months. Patients with high anastomoses exhibited significantly better role, emotional and social function, had a better body image and sexual function, fewer problems with defecation and lower frequency of diarrhea, as well as fewer chemotherapy-related side effects at 6 months postoperatively when compared with the low anastomosis group (all P<0.05). In conclusion, LLAR is generally acceptable for Chinese patients with rectal cancer, particularly for those with middle or high rectal cancer, in terms of functional outcome and quality of life.

Micro Structure of Injection Molding Machine Mold Clamping Mechanism: Design and Motion Simulation.

With the advent of intelligence, more and more machines and devices involve the creation of complex structures. In the intelligent manufacturing industries, moldings including injection molding, blow molding, compression molding and others play critical roles in manufacturing the highly precise parts required for building intelligent machines (such as computers, cell phones, robots, etc.). The performance of the clamping mechanism directly affects the quality of the microstructure of injection products. The design of injection molding mold clamping mechanism is based on the microstructure characteristics of the trip of toggle lever mechanism ratio, speed ratio, and force amplification ratio. These are used to study the main performance parameters, such as analysis, as well as for the establishment of the physical model of the clamping mechanism. The model is based on the microstructure of injection of hyperbolic elbow clamping mechanism kinematics simulation. Simulation results and the theoretical calculation contrast analysis shows that the maximum dynamic template speed is 215.34 mm/s. The dynamic templates and crosshead speed ratio is 2.15, therefore the design of injection molding mold clamping mechanism for microstructure provides favorable technical support. The method described here is important to build complicated molds required to build highly precise parts to build intelligent machineries.

Dual specificity phosphatase 5 is a novel prognostic indicator for patients with advanced colorectal cancer.

Dual specificity phosphatase 5 (DUSP5) is a negative regulator of Mitogen-activated protein kinase (MAPK) signaling pathway and has recently been identified as a tumor suppressor in several human malignancies. However, its clinical significance in colorectal cancer (CRC) remains unclear. In this study, we aimed to investigate the potential utility of DUSP5 as a novel biomarker for progression indication and chemotherapy benefit in CRC patients. Through quantitative real time-polymerase chain reaction and western blot, we determined that DUSP5 expression is dramatically lower in CRC tissues than that in matched normal tissues. The statistical analysis based on immunohistochemistry revealed that DUSP5 expression is significantly correlated with tumor differentiation, TNM stage, lymph node metastasis and distant metastasis. For the whole study cohort, patients with high DUSP5 expression had a better CRC-specific and disease-free survival than those with low DUSP5 expression and DUSP5 expression is an independent prognostic factor for patient survival. In subgroup analysis, DUSP5 has no prognostic significance in low-risk stage II patients, but could predict treatment response in high-risk stage II and stage III/IV patients who received standard FOLFOX chemotherapy scheme. Finally, the correlation analysis suggested that DUSP5 expression is associated with Epithelial-to-Mesenchymal Transition (EMT) phenotype in CRC tissues, suggesting that downregulated DUSP5 may contribute to poor prognosis partly by involving EMT. Taken together, our study proposes that DUSP5 is a promising biomarker for predicting CRC progression and advanced patients with high DUSP5 expression appear to benefit from standard FOLFOX chemotherapy scheme.

High expression of Zinc-finger protein X-linked promotes tumor growth and predicts a poor outcome for stage II/III colorectal cancer patients.

Zinc-finger protein X-linked (ZFX) was recently identified as a novel oncoprotein in several human malignancies. In this study, we examined the correlation between ZFX expression and the clinical characteristics of stage II/III CRC patients, as well as the molecular mechanism by which ZFX apparently contributes to CRC tumor progression. Using immunohistochemistry, we detected expression of ZFX in CRC tissues collected from stage II/III patients and determined that its expression correlated with tumor differentiation and stage. Survival analysis indicated that patients with high ZFX expression had poorer overall and disease-free survival. ZFX knockdown in SW620 and SW480 CRC cells significantly inhibited cell proliferation and colony formation, enhanced apoptosis and induced cell cycle arrest. It also enhanced the sensitivity of CRC cells to 5-Fu. In a xenograft model, ZFX knockdown suppressed in vivo CRC tumor growth. Microarray analysis revealed the primary target of ZFX to be DUSP5. Whereas ZFX knockdown increased DUSP5 expression, DUSP5 knockdown rescued ZFX-mediated cell proliferation in ZFX knockdown cells. These findings demonstrate that ZFX promotes CRC progression by suppressing DUSP5 expression and suggest that ZFX is a novel prognostic biomarker and potentially useful therapeutic target in stage II/III CRC patients.

The chemokine CXCL9 expression is associated with better prognosis for colorectal carcinoma patients.

The chemokine CXCL9 has been demonstrated to play an important role in the development of human malignancies. However, its prognostic significance in cancer patients remains unclear and less is known about its role in colonrectal carcinoma (CRC) patients. In this study, we found that the relative mRNA expression level of CXCL9 in primary colorectal tumor tissues was significantly higher than that in corresponding normal colon tissues. CXCL9 protein expression was also detected in 102 of 130 primary CRC patients by immunochemistry. Thus, CXCL9 might play a vital role in the progression of colorectal cancer. By analyzing the correlation between clinicopathological factors of patients and expression of CXCL9 protein, we showed that the expression of CXCL9 was significantly associated with tumor differentiation, tumor invasion, lymph node metastasis, distant metastasis, and vascular invasion, but not with other factors of CRC patients including age, gender, tumor location and tumor size. Furthermore, by performing Kaplan-Meier method as well as Cox's univariate and multivariate hazard regression model, we found that the higher the CXCL9 expression, the higher overall survival rate was observed, and CXCL9 expression was a significant independent prognostic factor for CRC patients. Therefore, CXCL9 is a useful predictor of better clinical outcome in CRC patients.

High expression of Zinc-finger protein X-linked is associated with reduced E-cadherin expression and unfavorable prognosis in nasopharyngeal carcinoma.

Zinc-finger protein X-linked (ZFX), a novel transcription factor required for self-renewal of embryonic stem cells, has recently been implicated in the initiation and progression of various human malignancies. However, its clinical significance in cancer patients remains largely inconclusive and its role in nasopharyngeal carcinoma (NPC) has never been reported. In this study, quantitative real-time polymerase chain reaction, Western blot and Immunohistochemistry were performed to detect ZFX expression in NPC and normal nasopharyngeal tissues. As a result, we found ZFX expression was significantly elevated in NPC tissues compared with that in normal nasopharyngeal tissues. The statistical analysis based on immunohistochemical staining demonstrated that ZFX expression was significantly correlated with lymph node stage and clinical stage. Furthermore, we found NPC patients with high ZFX expression had lower 5-year overall survival rates, progression-free survival rates, loco-regional relapse-free survival rates and distant metastasis-free survival rates than those with low ZFX expression (all P<0.05). The multivariate analysis indicated that ZFX expression was an independent prognostic factor for patients with NPC. More importantly, we also detected E-cadherin expression in NPC tissues and found it was inversely correlated with ZFX expression in NPC tissues, suggesting a potential involvement of ZFX in Epithelial-mesenchymal transition (EMT). Therefore, it is speculated that ZFX may promote NPC progression partly by regulating EMT. In summary, our study not only for the first time identified that ZFX could serve as an effective prognostic biomarker for NPC patients, but also suggested that targeting ZFX might be a novel therapeutic strategy for preventing NPC progression and metastasis.

N-cadherin, a novel prognostic biomarker, drives malignant progression of colorectal cancer.

Recent studies have indicated that the epithelial-mesenchymal transition (EMT) is a key molecular mechanism involved in the development of colorectal cancer (CRC). N-cadherin is a mesenchymal marker of the EMT and has been closely linked to several human malignancies. However, its role in CRC has remained elusive. In the present study, qRT-PCR and western blot analysis indicated that N-cadherin expression was higher in tumor tissues than in that in their adjacent normal tissues. Immunohistochemical evaluation of N-cadherin and E-cadherin (an epithelial marker of the EMT), indicated that N-cadherin expression was significantly associated with tumor differentiation, tumor size as well as tumor, nodes and metastasis stage. Correlation analysis suggested the expression of N-cadherin was negatively correlated with that of E-cadherin in CRC tissues. Kaplan-Meier analysis indicated that patients with high N-cadherin expression had a significantly lower overall survival and disease-free survival rate than those with low N-cadherin expression, while the opposite was found for E-cadherin. Of note, the present study found that high N-cadherin expression was an independent prognostic factor for CRC. In vitro assays showed that N-cadherin was widely expressed in CRC cell lines and silencing of N-cadherin suppressed the proliferation and migration of the CRC cell line HT-29 by upregulating E-cadherin, suggesting a potential role of N-cadherin in inducing EMT. In conclusion, the present study suggested that N-cadherin has the potential of serving as a novel prognostic predictor and a promising therapeutic target for CRC.

Overexpression of Tbx3 is correlated with Epithelial-Mesenchymal Transition phenotype and predicts poor prognosis of colorectal cancer.

AIMS: To investigate the clinical significance of Tbx3 in colorectal cancer (CRC) and the possible association between Tbx3 expression and Epithelial- Transition Mesenchymal (EMT) phenotype. METHODS: Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and western blotting were employed to evaluate the expression of Tbx3 in 30 fresh CRC and matched normal tissues. Using immunochemistry, protein level of Tbx3 and EMT markers (E-cadherin and N-cadherin) were identified in 150 pairs of paraffin-embedded specimen. RESULTS: The results of qRT-PCR and western blotting showed that Tbx3 expression was higher in CRC tissues than in corresponding normal tissues. The statistical analysis based on immunohistochemical evaluation suggested that Tbx3 aberrant expression was significantly associated with tumor size (P=0.049), differentiation (P=0.032), invasion (P=0.019), lymph node metastasis (P=0.049) and TNM stage (P=0.018). Patients who displayed high expression of Tbx3 may achieve a poorer overall survival (OS) and disease-free survival (DFS), compared to those with low expression of Tbx3. This tendency was also observed in patients with intermediate levels of disease (II and III stage). The multivariate analysis indicated Tbx3 expression could independently predict the outcome of CRC patients. Interestingly, correlation analysis suggested Tbx3 expression was negatively correlated with E-cadherin expression, but positively correlated with N-cadherin expression. CONCLUSION: Tbx3 may promote CRC progression by involving EMT program and has the potential to be an effective prognostic predictor for CRC patients.

Knockdown of Y­box­binding protein­1 inhibits the malignant progression of HT­29 colorectal adenocarcinoma cells by reversing epithelial­mesenchymal transition.

Y­box binding protein­1 (YB­1) has been identified as an oncoprotein in various malignancies. The aim of this study was to investigate the biological role of YB­1 and its association with epithelial­to­mesenchymal transition (EMT) in colorectal cancer (CRC). The expression of YB­1 and three EMT­related proteins (E­cadherin, N­cadherin and vimentin) was analyzed in 80 CRC and matched normal tissue samples, by immunohistochemistry. The results indicated that the expression of YB­1 was higher in CRC tissue samples than that in matched normal controls and was significantly correlated with tumor differentiation, tumor invasion, lymph node metastasis and distant metastases. Furthermore, analysis showed that YB­1 expression was negatively correlated with E­cadherin and positively correlated with N­cadherin and vimentin expression. In vitro assays showed that knockdown of YB­1 inhibited the proliferation, apoptosis resistance, invasion and migration of the HT­29 CRC cell line. Of note, following knockdown of YB­1, E­cadherin expression was elevated whereas N­cadherin and vimentin expression was reduced. Taken together, these results suggest that YB­1 promotes the malignant progression of CRC in part through the induction of EMT, and YB­1 may therefore be a potential novel target for CRC treatment.