Predictive Value of Magnetic Resonance Imaging Multi-parametric Analysis for Malignant Transformation of Sinonasal Inverted Papilloma: A Comprehensive Prediction Model.

OBJECTIVE: Accurate preoperative prediction of sinonasal inverted papilloma (SNIP) malignant transformation is essential and challenging. In this study, 3.0T magnetic resonance was used for qualitative, quantitative, and multi-parametric analysis to evaluate the predictive value of magnetic resonance imaging (MRI) in malignant transformation. METHODS: The data of patients with SNIP (n=83) or SNIP-transformed squamous cell carcinoma (SNIP-SCC) (n=21) were analysed retrospectively. Univariate analysis and multivariate logistic regression were used to establish models to predict the risk factors for the malignant transformation of SNIP. Receiver operating characteristic (ROC) curves were used to evaluate the ability of independent risk factors and related combination models to predict the malignant transformation of SNIP. RESULTS: Convoluted cerebriform pattern (CCP) mutation, apparent diffusion coefficient ratio (ADCr), and wash-in index (WII) 2 and 3 were independent risk factors for predicting malignant transformation of SNIP, with area under the ROC curve (AUC) values of 0.845, 0.862, 0.727, and 0.704, respectively. The AUC of the quantitative parameter model combined with ADCr and WII 2 and 3 was 0.910 for diagnosing malignant transformation. The AUC of the comprehensive model comprising all independent risk factors was 0.937, with a sensitivity, specificity, and accuracy of 90.48%, 90.36%, and 92.31%, respectively. CONCLUSION: Compared with assessing independent risk factors of CCP mutation, ADCr and WII, and the quantitative parameter model, the comprehensive model could improve the differential diagnosis ability of SNIP and SNIP-SCC, which provides an important imaging basis for the possible accurate preoperative evaluation of the malignant transformation of SNIP.

EGR1 Overexpression Inhibits the Occurrence of Preeclampsia by Binding to MicroRNA-574 Promoter and Upregulating GAB1.

Early growth response protein 1 (EGR1) is potent in modulating placental trophoblast cell growth and shows a differential expression in preeclampsia (PE). We aimed to identify the downstream mechanism of EGR1 in PE. RT-qPCR showed EGR1 was significantly decreased in PE placenta. Overexpression of EGR1 facilitated the proliferation and invasion of HTR-8/Svneo cells, and reduced the concentration of human chorionic gonadotrophin (HCG) in the supernatant. Bioinformatics prediction, ChIP, and luciferase reporter experiments revealed that EGR1 inhibited miR-574 expression by binding to miR-574 promoter and that miR-574 targeted GAB1. Furthermore, overexpression of miR-574 inhibited the proliferation and invasion of HTR-8/Svneo cells. GAB1 was downregulated in placenta of PE patients, which was positively correlated with EGR1 and negatively correlated with miR-574. Inhibition of GAB1 attenuated the effect of EGR1 overexpression on the proliferation and invasion of HTR-8/Svneo cells. All in all, EGR1 upregulated GAB1 by inhibiting miR-574, thus contributing to trophoblast cell proliferation and invasion.

Downregulation of receptor tyrosine kinase-like orphan receptor 1 in preeclampsia placenta inhibits human trophoblast cell proliferation, migration, and invasion by PI3K/AKT/mTOR pathway accommodation.

INTRODUCTION: Invasive deficiency of the trophoblast and poor remodeling of the uterine spiral arteries were probably the primary pathogenesis causes of preeclampsia (PE). The expression of receptor tyrosine kinase-like orphan receptor 1 (ROR1) during embryogenesis had been previously confirmed and was closely related to the function of tumor cells, which was similar to the characteristics of trophoblasts. In this work, we investigated the expression profile of ROR1 in preeclampsia placentas and the functional role of ROR1 in trophoblast cells, as well as the associated molecular mechanisms. METHODS: The localization expression of ROR1 in the placenta was detected by immunohistochemistry in 20 cases of normal term pregnancy, preterm delivery, late-onset severe PE, and early-onset severe PE, respectively. The expression levels were determined by fluorescence quantitative PCR and Western blot. The influence of ROR1 on trophoblast proliferation, migration, invasion, and potential regulatory pathways was evaluated in HTR-8/SVneo cell lines by transient transfection methods. RESULTS: The levels of ROR1 in the placental tissues in PE were significantly lower than those in normal term pregnancy and preterm delivery. Moreover, the expression levels of ROR1 in early-onset severe PE were significantly lower than those in its late counterparts. ROR1 overexpression increased cell proliferation, migration, and invasion of HTR-8/SVneo cells, whereas its silencing had the opposite effect. Meanwhile, the phosphorylation levels of critical kinases in the PI3K/AKT/mTOR pathways were increased by ROR1 overexpression, whereas they were decreased by the silencing of ROR1. CONCLUSION: ROR1 might be involved in the development of PE through regulating trophoblast viability, migration, and invasion by PI3K/AKT/mTOR signaling pathway.

Effects of forkhead box protein M1 on trophoblast invasion and its role in preeclampsia development.

The present study aimed to investigate the expression of the forkhead box protein M1 (FOXM1) in the placenta of patients with preeclampsia, and its effect on trophoblasts. A total of 28 patients with preeclampsia and 30 patients without preeclampsia (controls) who underwent cesarean section and were admitted to the Affiliated Hospital of Qingdao University between June 2013 and September 2016 were enrolled in the present study. The expression of FOXM1 in placental tissues was examined by reverse transcription-quantitative polymerase chain reaction, western blotting and immunohistochemistry. HTR8/SVneo cells were used to measure the in vitro expression of the vascular endothelial growth factor (VEGF). The results demonstrated that FOXM1 expression was downregulated in the placental tissues of patient with preeclampsia (P<0.05). Following the silencing of FOXM1 expression, the proliferation of HTR8/SVneo cells was suppressed. The results of flow cytometry demonstrated that proportion of HTR8/SVneo cells in the G0/G1 phase and the proportion of apoptotic cells increased. The expression of the apoptosis regulator BCL-2, as well as the expression of VEGF mRNA and protein expression were also downregulated following FOXM1 silencing. FOXM1 may therefore promote the development of preeclampsia via the VEGF signaling pathway.

Screening of differential proteins of placenta tissues in patients with pre-eclampsia by iTRAQ proteomics techniques.

BACKGROUND: Isotopically labeled relative and absolute quantification (iTRAQ) were applied together with liquid chromatogram-tandem mass spectrometry (LC-MS/MS) technique to screen and differentiate normal tissues and differential proteins of placenta tissue in the pre-eclampsia group, and to seek for a pre-eclampsia biomarker. METHODS: Thirty patients with severe pre-eclampsia (pre-eclampsia group) and 30 patients with normal full-term pregnancy (control group), who were admitted by the Obstetrical Department of The Affiliated Hospital of Qingdao University from December 2014 to June 2015, were collected for this study. Part of the placenta tissue was sampled following cesarean section to extract the total protein that was degenerated, reduced and enzymatically hydrolyzed. Following iTRAQ, mass spectroscopy was used for differentiation to obtain differential proteins in the expression. RESULTS: A total of 234 differential proteins were identified. The comparison between the severe pre-eclampsia group and the control group indicated over 1.5-folds of expression abundance difference (upregulation ratio >1.50, or downregulation ratio <0.67). The difference was statistically significant in 24 protein points in total, among which the expression of 14 protein points was upregulated compared with that of the control group, and the expression of 10 protein points was downregulated. CONCLUSIONS: iTRAQ combined with the LC-MS/MS technique can effectively screen differential proteins in placenta tissues of patients with pre-eclampsia.

Polymorphism-801G/A in the 3'-untranslated region of CXCL12 is not associated with preeclampsia in Chinese Han population.

OBJECTIVE: We investigated whether the CXCL12-801G/A polymorphism was associated with preeclampsia (PE) susceptibility in a Chinese Han population. METHODS: We examined 912 PE women and 1025 controls for the CXCL12-801G/A polymorphism by polymerase chain reaction (PCR) and correlations with clinical characteristics were examined. RESULTS: No significant differences in genotypic and allelic frequencies of CXCL12-G801A were found between cases and controls (genotype: χ2 = 2.095, p = 0.351; allele: χ2 = 1.713, p = 0.191). There were also no significant differences between early/late-onset or mild/severe PE and control groups. CONCLUSION: The results indicate that 801G/A in CXCL12 may not play a major role in pathogenesis of PE in a Chinese Han population.

Association between COMT Val158Met polymorphism and preeclampsia in the Chinese Han population.

OBJECTIVE: Previous studies have been indicated that catechol-O-methyltransferase gene (COMT) might play a significant role in the development of preeclampsia (PE). Our study aims to investigate the association between polymorphism in COMT with the susceptibility to PE in Chinese Han women. METHOD: A total of 1028 PE patients and 1399 normal pregnant women were enrolled. We detected the genotyping of COMT Val158Met loci by the TaqMan allelic discrimination real-time PCR . RESULTS: No significant difference in the genotypic and allelic distribution was found between the two groups (genotype: X2 = 0.583, p = 0.747; allele:X2 = 0.526, p = 0.468). CONCLUSION: The COMT Val158Met polymorphism might not be associated with PE in Chinese women.

Association between adiponectin receptor 1 gene polymorphism and insulin resistance in Chinese patients with polycystic ovary syndrome.

BACKGROUND/AIMS: Adiponectin receptor 1 (ADIPOR1) is an identified receptor for adiponectin, an adipocytokine with anti-inflammatory and insulin-sensitizing properties. The ADIPOR1 gene is a potential candidate gene in polycystic ovary syndrome (PCOS). The aim of this study is to assess the association between single-nucleotide polymorphism (SNP) rs1539355 in the ADIPOR1 gene and PCOS in Chinese women. METHODS: 302 patients with PCOS and 312 healthy controls were included in this study. The ADIPOR1 genotype distribution was detected using the polymerase chain reaction melting temperature shift method. RESULTS: The genotypic distributions of SNP rs1539355 did not differ in patients with PCOS compared to controls. However, the frequency of the G allele in the PCOS group was significantly higher than that in the control group (p = 0.037). Patients with the AG or GG genotype had a higher homeostasis model assessment for insulin resistance (HOMA-IR) (p < 0.05) compared to patients with the AA genotype. The fasting insulin levels in subjects with the GG genotype were significantly higher than those in patients with the AA genotype (p < 0.05). CONCLUSION: SNP rs1539355 in the ADIPOR1 gene is associated with insulin resistance in Chinese PCOS patients.

Genome-wide association study identifies eight new risk loci for polycystic ovary syndrome.

Following a previous genome-wide association study (GWAS 1) including 744 cases and 895 controls, we analyzed genome-wide association data from a new cohort of Han Chinese (GWAS 2) with 1,510 polycystic ovary syndrome (PCOS) cases and 2,016 controls. We followed up significantly associated signals identified in the combined results of GWAS 1 and 2 in a total of 8,226 cases and 7,578 controls. In addition to confirming the three loci we previously reported, we identify eight new PCOS association signals at P < 5 × 10(-8): 9q22.32, 11q22.1, 12q13.2, 12q14.3, 16q12.1, 19p13.3, 20q13.2 and a second independent signal at 2p16.3 (the FSHR gene). These PCOS association signals show evidence of enrichment for candidate genes related to insulin signaling, sexual hormone function and type 2 diabetes (T2D). Other candidate genes were related to calcium signaling and endocytosis. Our findings provide new insight and direction for discovering the biological mechanisms of PCOS.

Genome-wide association study identifies susceptibility loci for polycystic ovary syndrome on chromosome 2p16.3, 2p21 and 9q33.3.

Polycystic ovary syndrome (PCOS) is a common metabolic disorder in women. To identify causative genes, we conducted a genome-wide association study (GWAS) of PCOS in Han Chinese. The discovery set included 744 PCOS cases and 895 controls; subsequent replications involved two independent cohorts (2,840 PCOS cases and 5,012 controls from northern Han Chinese; 498 cases and 780 controls from southern and central Han Chinese). We identified strong evidence of associations between PCOS and three loci: 2p16.3 (rs13405728; combined P-value by meta-analysis P(meta) = 7.55 × 10⁻²¹, odds ratio (OR) 0.71); 2p21 (rs13429458, P(meta) = 1.73 × 10⁻²³, OR 0.67); and 9q33.3 (rs2479106, P(meta) = 8.12 × 10⁻¹9, OR 1.34). These findings provide new insight into the pathogenesis of PCOS. Follow-up studies of the candidate genes in these regions are recommended.