Cross-sectional and longitudinal associations between lipid accumulation product and hyperuricemia.

BACKGROUND AND AIMS: Lipid accumulation product (LAP) is a novel, sex-specific, index-describing lipid over accumulation. Previous studies used baseline LAP for predicting hyperuricaemia; however, the relationship between them is unclear. We aimed to investigate the relationship between LAP and the risk of hyperuricaemia in the Central Chinese population. METHODS AND RESULTS: This large-scale observational study comprised a cross-sectional population sample and a prospective cohort of 44,294 healthy subjects. This study examined the association between LAP and the risk of hyperuricaemia in the total sample and subgroups using multiple logistic regression analysis and multivariate cox proportional hazards model analysis. As a result, there was a dose-response relationship between LAP and the risk of hyperuricaemia. The prevalence of hyperuricaemia was 13.4% in the cross-sectional study. During 9 years of follow-up, hyperuricaemia occurred in 928 (19.8%) participants. The corresponding hazard ratios after multiple adjustments of hyperuricaemia in the second, third and fourth quartile were 1.34 (95% confidence interval [CI], 1.04-1.72), 2.01 (95% CI, 1.54-2.63), and 2.44 (95% CI, 1.80-3.30)-fold higher vs. the first quartile, respectively. Subgroup analyses showed that the association between LAP and the risk of hyperuricaemia was more pronounced in females, individuals≤49 years old and subjects with eGFR ≥60 ml/min/1.73 m2. CONCLUSION: LAP was positively related to the risk of hyperuricaemia in the Central Chinese population, particularly in women, individuals≤49 years old and adults with relatively normal renal function. These findings suggested the potential of LAP as an independent risk indicator in preventing hyperuricaemia.

Clinical Characteristics Predict Recurrence in Borderline Ovarian Tumor Patients with Fertility-Preserving Surgery.

PURPOSE: To identify prognostic factors in patients with borderline ovarian tumor (BOT) and establish and validate a nomogram predicting recurrence in BOT patients treated with fertility-preserving surgery. PATIENTS AND METHODS: Patients with BOT who underwent surgery at two institutions between January 2000 and June 2017 were included and categorized into training and validation cohorts. Univariate log rank test and Cox regression analysis were performed in the training cohort to identify prognostic factors, and a nomogram was developed to predict the recurrence rate. The model was validated by calculating the C-index and drawing the calibration curve and receiver operating curve (ROC). CONCLUSION: In the multivariate Cox regression analysis, practice period, past history of benign ovarian disease, past history of benign breast disease, elevated CA125 levels, elevated CA199 levels, surgical methods, greater omentum resection, FIGO stage, postoperative pregnancy, and re-operation were independently associated with recurrence-free survival (p<0.05). The aforementioned prognostic factors were used to develop a nomogram. The nomogram demonstrated a good ability to predict the risk of recurrence (training cohort C-index: 0.866, validation cohort C-index: 0.920). The calibration curve suggested that the predicted recurrence-free survival was closely related to the actual recurrence. ROC analysis showed that the nomogram had a good discriminatory power with the area under curve between 0.776 and 0.956. The nomogram can predict the 1-, 3-, and 5-year recurrence-free survival of BOT patients undergoing fertility-preserving surgery. The predictive model can help guide surgical plans, postoperative monitoring, and prognostic evaluation of BOT patients.

Identification of significant genes signatures and prognostic biomarkers in cervical squamous carcinoma via bioinformatic data.

BACKGROUND: Cervical squamous cancer (CESC) is an intractable gynecological malignancy because of its high mortality rate and difficulty in early diagnosis. Several biomarkers have been found to predict the prognose of CESC using bioinformatics methods, but they still lack clinical effectiveness. Most of the existing bioinformatic studies only focus on the changes of oncogenes but neglect the differences on the protein level and molecular biology validation are rarely conducted. METHODS: Gene set data from the NCBI-GEO database were used in this study to compare the differences of gene and protein levels between normal and cancer tissues through significant pathway selection and core gene signature analysis to screen potential clinical biomarkers of CESC. Subsequently, the molecular and protein levels of clinical samples were verified by quantitative transcription PCR, western blot and immunohistochemistry. RESULTS: Three differentially expressed genes (RFC4, MCM2, TOP2A) were found to have a significant survival (P < 0.05) and highly expressed in CESC tissues. Molecular biological verification using quantitative reverse transcribed PCR, western blotting and immunohistochemistry assays exhibited significant differences in the expression of RFC4 between CESC and para-cancerous tissues (P < 0.05). CONCLUSION: This study identified three potential biomarkers (RFC4, MCM2, TOP2A) of CESC which may be useful to clarify the underlying mechanisms of CESC and predict the prognosis of CESC patients.

Development and Validation of an RNA-Binding Protein-Based Prognostic Model for Ovarian Serous Cystadenocarcinoma.

Ribonucleic acid-binding proteins (RBPs) are reportedly involved in tumor progression and recurrence; however, the functions and mechanisms of action of RBPs in ovarian serous cystadenocarcinoma (OSC) are not known. To address these issues, gene expression profiles of OSC tissues from The Cancer Genome Atlas (TCGA) and normal tissues from the Genotype-Tissue Expression database were compared in order to identify RBPs that are differentially expressed in OSC. We also analyzed the biological functions of these RBPs and their relationship to clinical outcome. There were 190 RBPs that were differentially expressed between OSC and normal tissues, including 93 that were upregulated and 97 that were downregulated. Five of the RBPs were used to construct a prediction model that was evaluated by univariate and multivariate Cox regression analyses. TCGA data were randomly divided into training and test cohorts, and further categorized into high- and low-risk groups according to risk score in the model. The overall survival (OS) of the high-risk group was shorter than that of the low-risk group (training cohort P = 0.0007596; test cohort P = 0.002219). The area under the receiver operating characteristic curve of the training and test cohorts was 0.701 and 0.638, respectively, demonstrating that the model had good predictive power. A nomogram was established to quantitatively describe the relationship between the five prognostic RBPs and OS in OSC, which can be useful for developing individualized management strategies for patients.

Clinical Significance, Cellular Function, and Potential Molecular Pathways of CCT7 in Endometrial Cancer.

Objective: Endometrial cancer (EC) is a common gynecologic malignancy; myometrial invasion (MI) is a typical approach of EC spreads and an important index to assess tumor metastasis and outcome in EC patients. CCT7 is a member of the TCP1 chaperone family, involved in cytoskeletal protein folding and unfolding. In this study, the role of CCT7 in EC development was investigated. Methods: Clinical data for 87 EC cases and expression of CCT7 were analyzed. CCT7 was knocked out using siRNA-CCT7 in Ishikawa and RL95-2 cells, and their function about proliferation, apoptosis, and invasion was further tested. Bioinformatics methods were used to predict the potential pathways of CCT7 in EC development. Results: The rates of CCT7-positive cells in EC and adjacent normal endometrium tissues had a significant difference (67.8 vs. 51.4%, p = 0.035), and the expression rate increased from low to high pathological stage (39.7% in the I/II stage, 71.4% in the III/IV stage, p = 0.029). A similar change was found in protein level. CCT7 expression differed significantly between the deep MI group (>1/2) and the superficial MI group (≤1/2) (p = 0.039). However, there were no differences with respect to age, pathological type, and histological grade. CCT7 suppression induced a function loss in both Ishikawa and RL95-2 cells. Bioinformatics analysis demonstrated that EC patients with lower-level CCT7 expression had better overall survival (p = 0.0081). Gene ontology enrichment indicated that "RNA binding," "Mitochondrion," "Translation," and "Spliceosome" were most significantly enriched potential pathways. Five hub genes, PSMA5, PSMD14, SNRPB, SNRPG, and TXNL4A, were all significantly upregulated in EC and had a positive correlation with CCT7. Conclusions: CCT7 may be involved in EC development by excessively activating tumor cell function to promote MI or distant/nodal metastasis, which may contribute to the prognosis of EC patients.

Four Surgical Strategies for the Treatment of Cesarean Scar Defect: A Systematic Review and Network Meta-analysis.

OBJECTIVE: This network meta-analysis compared treatment via laparoscopy, hysteroscopy (HP), combined laparoscopy with HP (LH), and vaginal repair (VR) for reducing intermittent abnormal uterine bleeding and cesarean scar defect (CSD) diverticulum depth in patients with CSD. DATA SOURCES: Electronic databases (PubMed, EMBASE, The Cochrane Central Register of Controlled Trials, MEDLINE, ClinicalTrials.gov, Chinese Biomedical Literature Database, and China National Knowledge Integrated) were searched for articles published through June 13, 2018. METHODS OF STUDY SELECTION: The search included randomized controlled trials (RCTs) and observational studies of surgical treatment for CSD. Standardized mean difference (SMD) and 95% confidence intervals (CIs) were reported. RCTs were evaluated by the Cochrane risk-of-bias tool, observational studies by Risk of Bias in Nonrandomized Studies of Intervention, and overall evidence quality by grade. Data were analyzed by STATA (version 15.0; StataCorp, College Station, TX) and R software for windows (version 3.5.0; R Core Team, 2018). TABULATION, INTEGRATION, AND RESULTS: Ten studies (n = 858; 4 RCTs and 6 observational studies) were included. Patients who underwent uterine diverticulum resection by LH had a shorter duration of abnormal uterine bleeding than those by HP (SMD = 1.36, 95% CI, 0.37-2.36; p = .007) and VR (SMD = 1.58, 95% CI, 0.97-2.19; p <.0001). LH reduced the CSD diverticulum depth more than VR (SMD = 1.57, 95% CI, 0.54-2.61; p = .003). There was no significant difference in efficacy among the surgical procedures. CONCLUSION: LH reduced intermittent abnormal uterine bleeding and scar depth more than the other surgical interventions. Larger clinical trials are warranted to verify this analysis.

Identification of HSPA8 as a candidate biomarker for endometrial carcinoma by using iTRAQ-based proteomic analysis.

Although there are advances in diagnostic, predictive, and therapeutic strategies, discovering protein biomarker for early detection is required for improving the survival rate of the patients with endometrial carcinoma. In this study, we identify proteins that are differentially expressed between the Stage I endometrial carcinoma and the normal pericarcinous tissues by using isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis. Totally, we screened 1,266 proteins. Among them, 103 proteins were significantly overexpressed, and 30 were significantly downexpressed in endometrial carcinoma. Using the bioinformatics analysis, we identified a list of proteins that might be closely associated with endometrial carcinoma, including CCT7, HSPA8, PCBP2, LONP1, PFN1, and EEF2. We validated the gene overexpression of these molecules in the endometrial carcinoma tissues and found that HSPA8 was most significantly upregulated. We further validated the overexpression of HSPA8 by using immunoblot analysis. Then, HSPA8 siRNA was transferred into the endometrial cancer cells RL-95-2 and HEC-1B. The depletion of HSPA8 siRNAs significantly reduced cell proliferation, promoted cell apoptosis, and suppressed cell growth in both cell lines. Taken together, HSPA8 plays a vital role in the development of endometrial carcinoma. HSPA8 is a candidate biomarker for early diagnosis and therapy of Stage I endometrial carcinoma.

The anti-chemoresistant effect and mechanism of MUC1 aptamer-miR-29b chimera in ovarian cancer.

OBJECTIVE: Currently, there are no effective therapies for advanced ovarian cancer. In this study, we aim to determine the anti-tumor effect of MUC1 aptamer-miR-29b chimera in xenograft ovarian cancer models and chemo-resistance tumor model and to further explore the associated mechanism. METHODS: Xenograft ovarian cancer animal models were established using OVCAR-3, OVCA420, and OVCAR-3-Taxol cancer cells. The chimera (Chi-29b) was delivered through intraperitoneal injections. Tumor growth was evaluated. Gene expression and PTEN methylation were measured. RESULTS: We demonstrated that intratumoral injection of Chi-29b chimera significantly inhibited the growth of xenograft OVCAR-3 tumors through downregulating PTEN methylation, subsequent PTEN expression, as well as downregulating MAPK 4 and IGF1 expressions. In contrast, Chi-29b inhibited tumor growth in OVCA420 tumors by downregulating MAPK 4 & 10 and IGF1 expression without affecting PTEN expression. Intraperitoneal injection of Chi-29b significantly increased apoptosis in paclitaxel-resistant OVCAR-3 cells and inhibited the growth of xenograft OVCAR-3-Taxol tumors. The anti-chemoresistant role of Chi-29b in OVCAR-3-Taxol tumors was associated with the activation of PTEN signaling and downregulation of MAPK 4 and 10 and IGF1 expression. CONCLUSION: Our study indicated that Chi-29b chimera can effectively exert an anti-tumor effect in xenograft tumor models and an anti-chemoresistant role through inhibiting cancer stem cell activation.

Anticancer role of MUC1 aptamer-miR-29b chimera in epithelial ovarian carcinoma cells through regulation of PTEN methylation.

Ovarian cancer has a poor prognosis and advanced ovarian cancer lacks effective therapy. In this study, we seek to establish targeting therapy for ovarian cancer through tumor tissue-specific delivery of miRNA-29b to reexpress PTEN tumor-suppressor gene. A chimera (Chi-29b) was constructed to compose of a mucin 1 (MUC1) aptamer targeting tumor cell surface MUC1 protein and miR-29b inhibiting DNA methyltransferases' expression, subsequently reexpressing PTEN gene. The specificity and efficacy of the chimera delivery were analyzed in OVCAR-3 ovarian tumor cells, and the biological activities of the chimera were identified by the expression of its downstream molecules and cell apoptosis. We demonstrated that Chi-29b chimera can be specifically delivered into OVCAR-3 cells in a concentration-dependent manner. Dicer efficiently cleaved the Chi-29b chimera to release miR-29b. Chi-29b chimera downregulated Dnmt1, Dnmt3a, and Dnmt3b protein levels; induced hypomethylation in PTEN promoter; and upregulated PTEN mRNA and protein expression in OVCAR-3 cells. Importantly, Chi-29b chimera significantly induced apoptosis in OVCAR-3 cells. Our study indicated that Chi-29b chimera can effectively exert antitumor effect through specific delivery of miR-29b into OVCAR-3 tumor cells, subsequently reexpressing PTEN gene and inducing cell apoptosis.