Unveiling non-classical glycosylation patterns in Bombyx mori nucleopolyhedrovirus GP64: Insights into viral entry and fusion.

The glycoprotein GP64 of alphabaculovirus is crucial for viral entry and fusion. Here, we investigated the N-glycosylation patterns of Bombyx mori nucleopolyhedrovirus (BmNPV) GP64 and its signal peptide (SP) cleaved form, SPΔnGP64, along with their impacts on viral infectivity and fusogenicity. Through deglycosylation assays, we confirmed N-glycosylation of BmNPV GP64 on multiple sites. Mutational analysis targeting predicted N-glycosylation sites revealed diverse effects on viral infectivity and cell fusion. Particularly noteworthy were mutations at sites 175, which resulted in complete loss of infectivity and fusion capacity. Furthermore, LC-MS/MS analysis uncovered unexpected non-classical N-glycosylation sites, including N252, N302, N367, and N471, with only N302 and N471 identified in SPΔnGP64. Subsequent investigation highlighted the critical roles of these residues in BmNPV amplification and fusion, underscoring the essentiality of N367 glycosylation for GP64 fusogenicity. Our findings provide valuable insights into the non-classical glycosylation landscape of BmNPV GP64 and its functional significance in viral biology.

The maternal drug exposure birth cohort (DEBC) in China.

Drug exposure during pregnancy lacks global fetal safety data. The maternal drug exposure birth cohort (DEBC) study, a prospective longitudinal investigation, aims to explore the correlation of maternal drug exposure during pregnancy with pregnancy outcomes, and establish a human biospecimen biobank. Here we describe the process of establishing DEBC and show that the drug exposure rate in the first trimester of pregnant women in DEBC (n = 112,986) is 30.70%. Among the drugs used, dydrogesterone and progesterone have the highest exposure rates, which are 11.97% and 10.82%, respectively. The overall incidence of adverse pregnancy outcomes is 13.49%. Dydrogesterone exposure during the first trimester is correlated with higher incidences of stillbirth, preterm birth, low birth weight, and birth defects, along with a lower incidence of miscarriage/abortion. Due to the limitations of this cohort study, causative conclusions cannot be drawn. Further follow-up and in-depth data analysis are planned for future studies.

Optimization of Diagnosis-Related Groups for 14,246 Patients with Uterine Leiomyoma in a Single Center in Western China Using a Machine Learning Model.

Background: Uterine leiomyoma (UL) is one of the most common benign tumors in women, and its incidence is gradually increasing in China. The clinical complications of UL have a negative impact on women's health, and the cost of treatment poses a significant burden on patients. Diagnosis-related groups (DRG) are internationally recognized as advanced healthcare payment management methods that can effectively reduce costs. However, there are variations in the design and grouping rules of DRG policies across different regions. Therefore, this study aims to analyze the factors influencing the hospitalization costs of patients with UL and optimize the design of DRG grouping schemes to provide insights for the development of localized DRG grouping policies. Methods: The Mann-Whitney U-test or the Kruskal-Wallis H-test was employed for univariate analysis, and multiple stepwise linear regression analysis was utilized to identify the primary influencing factors of hospitalization costs for UL. Case combination classification was conducted using the exhaustive chi-square automatic interactive detection (E-CHAID) algorithm within a decision tree framework. Results: Age, occupation, number of hospitalizations, type of medical insurance, Transfer to other departments, length of stay (LOS), type of UL, admission condition, comorbidities and complications, type of primary procedure, other types of surgical procedures, and discharge method had a significant impact on hospitalization costs (P<0.05). Among them, the type of primary procedure, other types of surgical procedures, and LOS were the main factors influencing hospitalization costs. By incorporating the type of primary procedure, other types of surgical procedures, and LOS into the decision tree model, patients were divided into 11 DRG combinations. Conclusion: Hospitalization costs for UL are mainly related to the type of primary procedure, other types of surgical procedures, and LOS. The DRG case combinations of UL based on E-CHAID algorithm are scientific and reasonable.

RNA N6-methyladenosine of DHAPAT and PAP involves in regulation of diapause of Bombyx mori via the lipid metabolism pathway.

Environment-induced epigenetics are involved in diapause regulation, but the molecular mechanism that epigenetically couples nutrient metabolism to diapause regulation remains unclear. In this study, we paid special attention to the significant differences in the level of N6-adenosine methylation (m6A) of dihydroxyacetone phosphate acyltransferase (DHAPAT) and phosphatidate phosphatase (PAP) genes in the lipid metabolism pathway of the bivoltine silkworm (Bombyx mori) strain Qiufeng developed from eggs incubated at a normal temperature (QFHT, diapause egg producer) compared to those from eggs incubated at a low temperature (QFLT, non-diapause egg producer). We knocked down DHAPAT in the pupal stage of the QFLT group, resulting in the non-diapause destined eggs becoming diapausing eggs. In the PAP knockdown group, the colour of the non-diapause destined eggs changed from light yellow to pink 3 days after oviposition, but they hatched as normal. Moreover, we validated that YTHDF3 binds to m6A-modified DHAPAT and PAP mRNAs to promote their stability and translation. These results suggest that RNA m6A methylation participates in the diapause regulation of silkworm by changing the expression levels of DHAPAT and PAP and reveal that m6A epigenetic modification can be combined with a lipid metabolism signal pathway to participate in the regulation of insect diapause traits, which provides a clearer image for exploring the physiological basis of insect diapause.

Using 2D/3D ultrasound observation of endometrial thickness, endometrial volume, and blood flow changes to predict the outcome of frozen embryo transfer cycles: a prospective study.

Background: Endometrial thickness (EMT) and blood flow are commonly used indicators of endometrial receptivity. However, the results of single ultrasound examination studies differ. Therefore, we used 3-dimensional (3D) ultrasound to study the influence of changes in EMT, endometrial volume, and endometrial blood flow on frozen embryo transfer cycles. Methods: This was a prospective cross-sectional study. Women who underwent in vitro fertilization (IVF) at Dalian Women and Children's Medical Group and met the inclusion criteria were enrolled between September 2020 and July 2021. Ultrasound examinations were performed in patients who underwent frozen embryo transfer cycles on the day of progesterone administration, the third day after progesterone administration, and the day of embryo transplantation. Two-dimensional ultrasound was used to record EMT, 3D ultrasound was used to record endometrial volume, and 3D power Doppler ultrasound imaging was used to record the following endometrial blood flow parameters: vascular index, flow index, and vascular flow index. Changes in the 3 inspections of the EMT, volume, vascular index, flow index, and vascular flow index and 2 inspections of estrogen levels were categorized as "declining" or "nondeclining". The relationship between changes in a certain indicator and the IVF outcome was analyzed by univariate analysis and multifactorial stepwise logistic regression. Results: In total, 133 patients were enrolled in this study, 48 were excluded, and 85 were included in the statistical analysis. Among these 85 patients, 61 were pregnant (71%), 47 had a clinical pregnancy (55%), and 39 had an ongoing pregnancy (45%). The results showed that if the first change in endometrial volume was nondeclining, the outcomes of clinical and ongoing pregnancies were more likely to be unfavorable (P=0.03, P=0.01). Additionally, if the second change in endometrial volume on the day of embryo transplantation was nondeclining, the outcome of an ongoing pregnancy was more likely to be favorable (P=0.03). Conclusions: The changes in endometrial volume was a factor helpful in predicting the IVF outcome, whereas the changes in EMT and endometrial blood flow analyses were not helpful in predicting IVF outcome.

Exorista sorbillans (Diptera: Tachinidae) parasitism shortens host larvae growth duration by regulating ecdysone and juvenile hormone titers in Bombyx mori (Lepidoptera: Bombycidae).

The tachinid fly, Exorista sorbillans, is a notorious ovolarviparous endoparasitoid of the silkworm, Bombyx mori, causing severe damage to silkworm cocoon industry. Silkworm larvae show typically precocious wandering behavior after being parasitized by E. sorbillans; however, the underlying molecular mechanism remains unexplored. Herein, we investigated the changes in the levels of 20-hydroxyecdysone (20E) and juvenile hormone (JH) titer, and they both increased in the hemolymph of parasitized silkworms. Furthermore, we verified the expression patterns of related genes, which showed an upregulation of 20E signaling and biosynthesis genes but a significant downregulation of ecdysone oxidase (EO), a 20E inactivation enzyme, in parasitized silkworms. In addition, related genes of the JH signaling were activated in parasitized silkworms, while related genes of the JH degradation pathway were suppressed, resulting in an increase in JH titer. Notably, the precocious wandering behavior of parasitized silkworms was partly recoverable by silencing the transcriptions of BmCYP302A1 or BmCYP307A1 genes. Our findings suggest that the developmental duration of silkworm post parasitism could be shortened by regulation of 20E and JH titers, which may help silkworm to resist the E. sorbillans infestation. These findings provide a basis for deeper insight into the interplay between silkworms and E. sorbillans and may serve as a reference for the development of a novel approach to control silkworm myiasis.

m6A-dependent mevalonate kinase in juvenile hormone synthesis pathway regulates the diapause process of bivoltine silkworm (Bombyx mori).

BACKGROUND: Research has shown that epigenetic modification are involved the regulation of diapause in bivoltine silkworms (Bombyx mori), but it remains unclear how epigenetic modification in response to environmental signals precisely to regulate the diapause processing of bivoltine B. mori. METHODS AND RESULTS: In this study, the diapause terminated eggs of bivoltine B. mori, Qiufeng (QF) were divided into two groups: a QFHT group incubated at 25 °C with a natural day/night cycle to produce diapause eggs, and a QFLT group incubated at 16.5 °C in darkness to produce non-diapause eggs. On the 3rd day of the pupal stage, the total RNAs of the eggs were extracted and their N6-adenosine methylation (m6A) abundances were analyzed to explore the effects of m6A methylation on diapause in the silkworm. The results showed that 1984 m6A peaks are shared, 1563 in QFLT and 659 in QFHT. The m6A methylation level of the QFLT group was higher than that of the QFHT one in various signaling pathways. The m6A methylation rate of mevalonate kinase (MK) in the insect hormone synthesis pathway was significantly different between the two groups. The knockdown of MK by RNA interference in the pupae of QFLT resulted in females laying diapause eggs rather than non-diapause eggs after mating. CONCLUSIONS: m6A methylation involves in the diapause regulation of bivoltine B. mori by changing the expression levels of MK. This result provides a clearer image of the environmental signals on the regulation of diapause in bivoltine silkworms.

Maternal environmental, occupational, and urinary metabolite levels of benzene compounds and their association with congenital heart diseases in offspring: a case‒control study in China.

The conclusions about the association of maternal pregnancy environment, occupation, and benzene compounds with fetal CHD are not entirely consistent. Eight hundred seven CHD cases and 1008 controls were included in this study. All occupations were classified and coded against the Occupational Classification Dictionary of the People's Republic of China (2015 version). Logistic regressions were used to explore the correlation among environmental factors, occupation types, and CHDs in offspring. We found that living near public facilities and having exposure to chemical reagents and hazardous substances were significant risk factors for CHDs in offspring. We found that offspring of mothers who worked in agriculture and similar work during pregnancy suffered from CHD. The risk of all CHDs in the offspring of pregnant women working in production manufacturing and related work was significantly higher than that in unemployed pregnant women, the risk was also observed in 4 subtypes of CHDs. We compared the concentrations of the five metabolite (MA, mHA, HA, PGA, and SPMA) levels of benzene compounds in the urine of mothers in case and control groups and found no significant differences. Our study suggests that maternal exposure during pregnancy and certain environmental and occupational conditions are risk factors for CHD in offspring, but did not support an association between concentrations of metabolites of benzene compounds in the urine of pregnant women and CHDs in their offspring.

A Study on the Prediction of Reproductive Outcomes in Frozen Embryo Transfer Cycles by Calculating the Volume of Uterine Junctional Zone with Three-Dimensional Ultrasound.

PURPOSE: To prospectively study the influence of the volume of the uterine junctional zone (JZ) as a novel predictor of reproductive outcomes in frozen embryo transfer cycles. METHODS: Among the first 30 patients, intra- and interobserver repeatability was evaluated and expressed as a coefficient of repeatability. The same classification system was used to evaluate the JZ of 142 infertility patients undergoing in vitro fertilization (IVF). Ultrasonography was performed on the day before transplantation. The three-dimensional (3D) volume images were then analyzed to obtain the volume of the endometrium (EV), the average thickness of the JZ on the coronal plane, and the volume of the JZ (JZV). The JZV was then divided by the EV. These parameters were compared with the outcomes of clinical pregnancy. RESULTS: The 3D image showed that the JZ achieved a good intra- and interobserver consistency (k = 0.862, k = 0.694). The total pregnancy rate was 47%. There was a highly significant difference between pregnant and non-pregnant women with respect to age (p < 0.001), JZV (p = 0.003), and JZV/EV (p < 0.001) on the day before transplantation. Age and JZV/EV were independent factors for predicting the success of IVF transplantation (p = 0.010, p = 0.016). The area under the ROC curve of JZV/EV in predicting clinical pregnancy was 0.688, the cut-off value was 0.54, the sensitivity was 83.8%, and the specificity was 50.0%. CONCLUSION: Age and JZV/EV are independent factors for predicting the success of frozen embryo transfer cycles in IVF. A smaller JZV/EV was more beneficial for clinical pregnancy.

PHLDA1 promotes glioblastoma cell growth via sustaining the activation state of Ras.

Activation of the Ras signaling pathway promotes the growth of malignant human glioblastoma multiforme (GBM). Mutations in Ras are rare in GBM, elevated levels of activated Ras are prevalently observed in GBM. However, the potential mechanism of how Ras is activated in GBM remains unclear. In this study, we screened a new interacted protein of Ras, PHLDA1. Our findings confirmed that PHLDA1 acted as an oncogene and promoted glioma progression and recurrence. We demonstrated that PHLDA1 was upregulated in GBM tissues and cells. PHLDA1 overexpression promoted cell proliferation and tumor growth. In terms of mechanism, PHLDA1 promoted cell proliferation by regulating Ras/Raf/Mek/Erk signaling pathway. Moreover, Src promotes GTPase activity of Ras via tyrosine 32 phosphorylation. PHLDA1 and Src competed for binding with Ras, inhibiting Ras phosphorylation by Src and rescuing Ras activity. This study may provide a new idea of the molecular mechanism underlying glioma progression and a novel potential therapeutic target for comprehensive glioblastoma treatment.

Validity of the association between five steroid hormones quantification and female infertility conditions: A new perspective for clinical diagnosis.

Quantification of endogenous steroids and their precursors is essential for diagnosis of a wide range of causes for female infertility. However, immunoassays often overestimate concentrations due to assay interference by other endogenous steroids, especially at low concentrations. In addition, it still lacks of diagnostic reference intervals for five sex steroid hormones, including estradiol (E2), 11-deoxycorticosterone (DOC), 17-hydroxyprogesterone (17-OHP4), pregnenolone (P5) and progesterone (P4), which are crucial for distinguishing between normal individuals and female infertility. Therefore, we developed and validated a reliable and rapid ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for simultaneous determination and quantification of five sex hormones, giving the reference intervals to accurately evaluate and diagnose female infertility. Our results showed that the developed UPLC-MS/MS assay was fast, high throughput, reproducible, specific, accurate, highly sensitive, and fully validated for simultaneous determination of P5, P4, 17-OHP4, DOC and E2 in human follicular fluid. The simple sample preparation procedure in the current study gave reproducible and consistent recoveries. The validation results show that the UPLC-MS/MS assay has acceptable accuracy and precision at low concentrations, which permits their use in clinical study. In addition, our data gave the concentration range of five steroid hormones quantification in patients with female infertility and normal individuals. Our data can be used to accurately evaluate and diagnose female infertility.

Association between congenital heart defects and maternal manganese and iron concentrations: a case-control study in China.

To investigate the correlation between maternal manganese and iron concentrations and the risk of CHD among their infant. A multi-center hospital-based case control study was conducted in China. There were 322 cases and 333 controls have been selected from pregnant women who received prenatal examinations. Correlations between CHDs and maternal manganese and iron concentrations were estimated by conditional logistic regression. Moreover, the interaction between manganese and iron on CHDs was analyzed. Compared with the controls, mothers whose hair manganese concentration was 3.01 µg/g or more were more likely to have a child with CHD than those with a lower concentration. The adjusted OR was 2.68 (95%CI = 1.44-4.99). The results suggested that mothers whose iron content was 52.95 µg/g or more had a significantly higher risk of having a child with CHD (aOR = 2.87, 95%CI = 1.54-5.37). No interaction between maternal manganese and iron concentrations was observed in the multiplicative or additive model. The concurrently existing high concentration of manganese and iron may bring higher risk of CHD (OR = 7.02). Women with excessive manganese concentrations have a significantly increased risk of having offspring with CHDs. The high maternal iron status also correlates with CHDs. The concurrently existing high concentration of manganese and iron may bring higher risk of CHD.

Lactobacillus spp. create a protective micro-ecological environment through regulating the core fucosylation of vaginal epithelial cells against cervical cancer.

Vaginal dysbiosis often occurs in patients with cervical cancer. The fucosylation of mucosal epithelial cells is closely related to microbial colonization, and play an important role in protecting the vaginal mucosal epithelial cells. However, no reports on the relationship between vaginal dysbiosis and abnormal mucosal epithelial cell fucosylation, and their roles in the occurrence and development of cervical cancer are unavailable. Here we report that core fucosylation levels were significantly lower in the serum, exfoliated cervical cells and tumor tissue of cervical cancer patients. Core fucosyltransferase gene (Fut8) knockout promoted the proliferation and migration of cervical cancer cells. In patients with cervical cancer, the vaginal dysbiosis, and the abundance of Lactobacillus, especially L. iners, was significantly reduced. Meanwhile, the abundance of L.iners was positively correlated with core fucosylation levels. The L. iners metabolite lactate can activate the Wnt pathway through the lactate-Gpr81 complex, which increases the level of core fucosylation in epidermal cells, inhibiting the proliferation and migration of cervical cancer cells, and have application prospects in regulating the vaginal microecology and preventing cervical cancer.

Unintended pregnancy-related factors and the occurrence of offspring congenital heart disease: a multi-site case-control study in China.

OBJECTIVES: The aim of this study was to explore the association between unintended pregnancy and related factors among congenital heart defects (CHDs) in infants. METHODS: A total of 1197 cases with isolated CHDs and 1125 controls without any abnormalities were analysed in this multicentre study at seven hospitals in China. According to the pregnancy intention, cases were divided into two groups: planned and unintended pregnancies. The adjusted odds ratio (AOR) was calculated by logistic regression analysis to assess the association between unintended pregnancy and CHD occurrence. The time to prepare for pregnancy and the influencing factors were also compared in this article. RESULTS: The risk for CHD occurrence was significantly associated with unintended pregnancy (AOR: 1.42; 95%CI: 1.16-1.73), which may increase the risks for each subtype of CHD occurrence. Risks such as parental smoking, housing renovation, accidental alcohol consumption, lack of health check-ups, and no folic acid supplementation before pregnancy were distributed differently among the planned and unintended pregnancy groups and were associated with CHD occurrence. However, there was no significant association between the duration of planned pregnancy and the risk of CHDs. CONCLUSIONS: Unintended pregnancy increased the risk of CHDs in infants. This risk may be related to some known and unknown factors. SYNOPSIS: Some unintended pregnancy related factors may increase the risk for foetal CHDs. The duration of planning pregnancy may not be associated with the risk of CHDs.

Mucinous breast carcinoma metastatic to thyroid gland: Report of a case diagnosed by fine-needle aspiration cytology.

Mucinous breast cancer is a slow-growing neoplasm, which has fewer lymph node metastases and favorable prognosis compared with invasive breast cancer no special type. The hematogenous spread of breast mucinous carcinoma is very rare. Though breast cancer involving thyroid has been reported before, there is still no report about thyroid metastatic breast mucinous carcinoma in the literature. Recently by performing thyroid fine-needle aspiration, a 58-year-old woman who had breast cancer 13 years ago was diagnosed as thyroid metastatic mucinous breast carcinoma, cellular variant with neuroendocrine differentiation. For this patient, the thyroid was the only involved site without widespread metastatic diseases, so thyroidectomy and the right cervical lymph nodes dissection were performed to make better survival. As a result, the patient had not shown any signs of recurrence 9 months after the thyroid surgery.

CELF2 suppresses non-small cell lung carcinoma growth by inhibiting the PREX2-PTEN interaction.

The phosphoinositide 3-kinase (PI3-K)/Akt signaling pathway is important in the regulation of cell proliferation through its production of phosphatidylinositol 3,4,5-triphosphate (PIP3). Activation of this pathway is frequently observed in human cancers, including non-small cell lung carcinoma. The PI3-K/Akt pathway is negatively regulated by the dual-specificity phosphatase and tensin homolog (PTEN) protein. PTEN acts as a direct antagonist of PI3-K by dephosphorylating PIP3. Studies have shown that PTEN phosphatase activity is inhibited by PREX2, a guanine nucleotide exchanger factor (GEF). Multiple studies revealed that CELF2, an RNA binding protein, cooperates synergistically with PTEN as a tumor suppressor in multiple cancers. However, the underlying mechanism as to how CELF2 enhances PTEN activity remains unclear. Here, we report that CELF2 interacts with PREX2 and reduces the association of PREX2 with PTEN. Consistent with this observation, PTEN phosphatase activity is upregulated with CELF2 overexpression. In addition, overexpression of CELF2 represses both Akt phosphorylation and cell proliferation only in the presence of PTEN. In an ex vivo study, CELF2 gene delivery could significantly inhibit patient-derived xenografts (PDX) tumor growth. To further investigate the clinical relevance of this finding, we analyzed 87 paired clinical lung adenocarcinoma samples and the results showed that CELF2 protein expression is downregulated in tumor tissues and associated with poor prognosis. The CELF2 gene is located on the chromosome 10p arm, a region frequently lost in human cancers, including breast invasive carcinoma, low-grade glioma and glioblastoma. Analysis of TCGA datasets showed that CELF2 expression is also associated with shorter patient survival time in all these cancers. Overall, our work suggests that CELF2 plays a novel role in PI3-K signaling by antagonizing the oncogenic effect of PREX2.

Clinicopathological and prognostic significance of FOXP3+ tumor infiltrating lymphocytes in patients with breast cancer: a meta-analysis.

BACKGROUND: The prognostic significance of FOXP3+ tumor-infiltrating lymphocytes (TILs) in patients with breast cancer remains controversial. The aims of our meta-analysis are to evaluate its association with clinicopathological characteristics and prognostic significance in patients with breast cancer. METHODS: PubMed, Embase, Cochrane Database and the Ovid Database were systematically searched (up to April 2015). The meta-analysis was performed using hazard ratio (HR), odds ratio (OR) and 95 % confidence intervals (CI) as effect measures. Using the random-effects model, statistical analysis was performed using Stata software, version 12.0. RESULTS: Seventeen studies including 8277 patients with breast cancer were analyzed. The meta-analysis indicated that the incidence difference of FOXP3+ TILs was significant when comparing the lymph node positive group to negative group (OR = 1.305, 95 % CI [1.071, 1.590]), the histological grade III group to the I-II group (OR = 3.067, 95 % CI [2.288, 4.111]), the ER positive group to the negative group (OR = 0.435, 95 % CI [0.287, 0.660]), the PR positive group to the negative group (OR = 0.493, 95 % CI [0.296, 0.822]), the HER2 positive group to the negative group (OR = 1.896, 95 % CI [1.335, 2.692]), the TNBC group to the non TNBC group (OR = 2.456, 95 % CI [1.801, 3.348]). The detection of FOXP3+ TILs was significantly correlated with the recurrence-free survival (RFS) of patients (HR = 1.752, 95 % CI [1.188-2.584]) and the overall survival (OS) of patients (HR =1.447, 95 % CI [1.037-2.019]). CONCLUSIONS: Our meta-analysis demonstrates that the presence of high levels of FOXP3+ TILs is associated with prognosis for breast cancer patients and predicts lymph node metastasis, hormone receptor and HER-2 status.

Differential ß-catenin expression levels are associated with morphological features and prognosis of colorectal cancer.

ß-catenin, an epithelial-mesenchymal transition (EMT)-associated marker, is key in the progression of colorectal cancer (CRC). However, the prognostic significance of ß-catenin expression in patients with CRC remains controversial. In the present study, the expression of ß-catenin at the tumor invasive front and the tumor center was investigated, and the correlations amongst ß-catenin differential expression patterns and the clinicopathological characteristics and prognosis of CRC patients were determined. In total, 181 patients that were diagnosed with CRC (as determined by histopathological evaluation) and subjected to surgical resection at the First Hospital of China Medical University between 2000 and 2001 were examined, and CRC specimens were obtained. Immunohistochemical (IHC) staining of ß-catenin was performed for each specimen. The nuclear ß-catenin expression levels were identified to be significantly lower in the tumor center than at the tumor invasive front (immunoreactivity score, 0.05±0.303 versus 2.18±3.917; P<0.001). The presence of nuclear ß-catenin overexpression at the tumor invasive front was found to be correlated with the tumor, node, metastasis stage (P=0.020), lymph node metastasis (P=0.016) and histological differentiation (P=0.006). Survival analysis revealed that reduced membranous expression levels and increased nuclear expression levels of ß-catenin were statistically significantly associated with poor survival times. Furthermore, differential ß-catenin expression levels were associated with aggressive morphological features, EMT and a poor prognosis in CRC. Therefore, IHC analysis of ß-catenin is considered to be a useful marker to predict the prognosis in patients with CRC.

The role of pleomorphic adenoma gene-like 2 in gastrointestinal cancer development, progression, and prognosis.

Numerous previous studies have revealed that pleomorphic adenoma gene-like 2 (PLAGL2) is a transcription factor that is active in cancer progression. The aim of this study was to investigate the role of PLAGL2 in the development, progression and prognosis of gastrointestinal cancer. Immunohistochemical analysis revealed that PLAGL2 was expressed in gastrointestinal tumors and adjacent normal tissues. The expression of PLAGL2 was significantly higher in 225 colorectal cancer tissues than in 66 adjacent non-tumor tissues (P = 0.037). However, expression was not significantly different between 286 gastric tumors and 57 adjacent non-tumor tissues (P = 0.352). Moreover, the PLAGL2 expression level significantly correlated with the depth of tumor invasion in colorectal cancer (P = 0.030). However, the PLAGL2 expression level significantly correlated with tumor size in gastric cancer (P = 0.046). Furthermore, we performed survival analyses and found that neither higher nor lower PLAGL2 expression was a prognostic factor in gastrointestinal cancer. Our findings indicate that PALGL2 serves as a tumor oncoprotein in the development and progression of colorectal cancer. However, the role of this protein in the development, progression and prognosis of gastric cancer is uncertain. Further investigation into the molecular mechanisms of PLAGL2 activity in gastrointestinal cancer is warranted.

ILEI: a novel marker for epithelial-mesenchymal transition and poor prognosis in colorectal cancer.

AIMS: Accumulating evidence over the past decade has shown that abnormal activation of epithelial to mesenchymal transition (EMT) contributes to tumour progression and metastasis in colorectal cancer (CRC). In this study, we investigated the expression of interleukin-like EMT inducer (ILEI) and EMT-associated markers (E-cadherin, vimentin) in CRC tissues and determined the correlations between ILEI expression and clinicopathological characteristics, prognosis and EMT in CRC. METHODS AND RESULTS: In total, 194 patients diagnosed with CRC based on histopathological evaluation and those subjected to surgical resection at the First Hospital of China Medical University between 2003 and 2005 were examined. Immunohistochemical staining for ILEI, vimentin and E-cadherin was performed for each specimen. Cytoplasmic overexpression of ILEI usually accompanied down-regulation of E-cadherin and positive expression of vimentin. Conversely, ILEI was simultaneously down-regulated with overexpression of E-cadherin and negative expression of vimentin. ILEI overexpression was associated significantly with T-stage, N-stage, TNM stage and EMT phenotype (P = 0.024, <0.001, <0.001 and <0.001, respectively). Multivariate analysis revealed that ILEI expression was an independent prognostic factor for patient survival. CONCLUSIONS: Our findings indicate that cytoplasmic ILEI expression is a potential marker of EMT and tumour progression in CRC. ILEI is an independent predictive factor associated with poor prognosis in CRC.