Analysis of the Secreted Peptidome from Omental Adipose Tissue in High-Grade Serous Ovarian Cancer.

High-grade serous ovarian cancer (HGSOC) is a preferential omental metastasis malignancy. Since omental adipose tissue is an endocrine organ, we used liquid chromatography tandem mass spectrometry (LC-MS/MS) to compare the peptides secreted from omental adipose tissues of HGSOC and benign serous ovarian cysts (BSOC). Among the differentially secreted peptides, we detected 58 upregulated peptides, 197 downregulated peptides, 24 peptides that were only in the HGSOC group and 20 peptides that were only in the BSOC group (absolute fold change ≥ 2 and P < 0.05). Then, the basic characteristics of the differential peptides were analyzed, such as lengths, molecular weights, isoelectric points, and cleavage sites. Furthermore, we summarized the possible functions according to the precursor protein functions of the differentially expressed peptides by Gene Ontology (GO) analysis with the Annotation, Visualization, and Integrated Discovery (DAVID) database and canonical pathway analysis with IPA. For the GO analysis, the differentially secreted peptides were mainly associated with binding in molecular function and cellular processes in biology process. For the canonical pathways, the differentially secreted peptides were related to calcium signaling, protein kinase A signaling, and integrin-linked kinase (ILK) signaling. We also identified 67 differentially secreted peptides that located in the functional domains of the precursor proteins. These functional domains were mainly related to energy metabolism and immunoregulation. Our study might provide drugs that could potentially treat HGSOC or omental metastases of HGSOC cells.

Diagnostic value of total testosterone and free androgen index measured by LC-MS/MS for PCOS and insulin resistance.

BACKGROUND: The objective of the study was to explore the clinical significance of steroid hormones in the diagnosis of PCOS and PCOS-related insulin resistance through liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) and chemiluminescent immunoassay (CLIA). METHODS: The study included 114 patients with PCOS and 100 controls. Steroid hormone levels in serum were measured using LC-MS/MS and CLIA. The Bland-Altman method was used to check the consistency between the two methods. The diagnostic value of the LC-MS/MS method for female hyperandrogenemia and PCOS was evaluated. RESULTS: Women with PCOS were younger than controls on average (p < 0.001). PCOS patients had higher luteal hormone (LH, p < 0.001), insulin (p = 0.002), estradiol (E2, p < 0.001), total testosterone (TT, p < 0.001), free androgen index (FAI, p = 0.021), dehydroepiandrosterone sulfate (DHEA, p = 0.021), insulin resistance index (HOMA-IR) (p = 0.034), and fasting glucose (p = 0.017) levels than controls as measured by CLIA. The diagnostic value of TT was the best, and the area under the AUC curve was 0.766. Women with PCOS had higher androstenedione (A2, p < 0.001), FAI (p < 0.001), TT (p < 0.001), and 17-hydroxyprogesterone (17-OHP, p < 0.001) levels than controls as measured by LC-MS/MS. The ROC curve showed that the diagnostic efficacy of A2, TT, and 17-OHP was 0.830, 0.851, and 0.714, respectively. The consistency of TT detected by LC-MS/MS and CLIA was poor according to the Bland-Altman method. Detected TT by LC-MS/MS had the highest diagnostic efficiency for PCOS. The diagnostic power of the LC-MS/MS results for PCOS-related insulin resistance was analyzed. The results showed that the FAI had the highest diagnostic power, with an ROC curve of 0.798. CONCLUSION: LC-MS/MS is more sensitive and accurate than CLIA in the determination of serum TT and FAI. TT is more effective for the diagnosis of PCOS, whereas FAI is more valuable in the diagnosis of insulin resistance.

Analysis of secreted peptidome from omental adipose tissue in polycystic ovarian syndrome patients.

Polycystic ovarian syndrome (PCOS) is a common endocrinopathy associated with increased risk of metabolic disorders. Prevalence of adiposity and obesity is greater in women suffering from PCOS. Moreover, adipose tissue dysfunction has been demonstrated in PCOS patients, particularly in abdominal adipose tissue. This dysfunction likely aggravates the metabolic and reproductive abnormalities. We used liquid chromatography-mass spectrometry to compare the peptides secreted from PCOS and non-PCOS abdominal adipose tissue. We detected 298 upregulated peptides and 31 downregulated peptides (absolute fold change ≥ 2 and p < 0.05). Twenty-nine peptides were only detected in the PCOS group, while 18 were only detected in the control group. In addition, we demonstrate that these cleavage products are not degradation products of the proteasome based on previous studies reported. Gene Ontology enrichment and pathway analysis were performed to study differentially secreted peptides through their precursor proteins. We identified 12 peptides from 10 precursor proteins associated with PCOS, and 6 peptide sequences were located in the functional domains of their corresponding precursor proteins. These results provide a deeper understanding of adipose tissue-derived peptides in PCOS for future functional studies.

A signature based on glycosyltransferase genes provides a promising tool for the prediction of prognosis and immunotherapy responsiveness in ovarian cancer.

BACKGROUND: Ovarian cancer (OC) is the most fatal gynaecological malignancy and has a poor prognosis. Glycosylation, the biosynthetic process that depends on specific glycosyltransferases (GTs), has recently attracted increasing importance due to the vital role it plays in cancer. In this study, we aimed to determine whether OC patients could be stratified by glycosyltransferase gene profiles to better predict the prognosis and efficiency of immune checkpoint blockade therapies (ICBs). METHODS: We retrieved transcriptome data across 420 OC and 88 normal tissue samples using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, respectively. An external validation dataset containing 185 OC samples was downloaded from the Gene Expression Omnibus (GEO) database. Knockdown and pathway prediction of B4GALT5 were conducted to investigate the function and mechanism of B4GALT5 in OC proliferation, migration and invasion. RESULTS: A total of 50 differentially expressed GT genes were identified between OC and normal ovarian tissues. Two clusters were stratified by operating consensus clustering, but no significant prognostic value was observed. By applying the least absolute shrinkage and selection operator (LASSO) Cox regression method, a 6-gene signature was built that classified OC patients in the TCGA cohort into a low- or high-risk group. Patients with high scores had a worse prognosis than those with low scores. This risk signature was further validated in an external GEO dataset. Furthermore, the risk score was an independent risk predictor, and a nomogram was created to improve the accuracy of prognostic classification. Notably, the low-risk OC patients exhibited a higher degree of antitumor immune cell infiltration and a superior response to ICBs. B4GALT5, one of six hub genes, was identified as a regulator of proliferation, migration and invasion in OC. CONCLUSION: Taken together, we established a reliable GT-gene-based signature to predict prognosis, immune status and identify OC patients who would benefit from ICBs. GT genes might be a promising biomarker for OC progression and a potential therapeutic target for OC.

Epidemiological investigation of urinary incontinence in peri- and postpartum women from Nanjing, China.

OBJECTIVES: We aimed to determine the prevalence of urinary incontinence (UI) during the peri- and postpartum period in women from Nanjing, China, and estimate its risk factors. METHODS: From January to December 2018, a total of 6500 postpartum women were enrolled and asked to complete the questionnaires. Of these, 6370 (98%) women returned the questionnaires with valid responses. Additional data were collected, including age, height, weight, gestation time and parity, and neonatal weight. The International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form was used. Surface electromyography (sEMG) and a biofeedback training system were used as a testing platform, and PESEMG values were obtained. RESULTS: The prevalence of UI during pregnancy and at 6 weeks postpartum in women was 29.76% and 12.50%, respectively. The prevalence of stress UI (SUI), urge UI (UUI), mixed UI (MUI), and other types of UI that developed during pregnancy was 25.48%, 1.66%, 1.65%, and 0.97%, respectively. The prevalence of SUI, UUI, MUI, and other types of UI at 6 weeks postpartum was 8.49%, 2.07%, 1.16%, and 0.77%, respectively. Multivariate analysis showed that advanced age, greater postpartum body mass index (BMI), macrosomia, multiparity, and vaginal delivery were risk factors of postpartum UI. Women with mild degree of UI in pregnancy, those who had undergone cesarean section, and those without UI before pregnancy were relieved from UI at 6 weeks postpartum. CONCLUSIONS: The rate of UI in peri- and postpartum women from Nanjing is consistent across China. The most common type of UI was SUI, with many risk factors affecting its occurrence. Advanced age, greater postpartum BMI, multiparity, macrosomia, and vaginal delivery might be the main risk factors of UI in postpartum women.

LncRNA HOXB-AS3 promotes growth, invasion and migration of epithelial ovarian cancer by altering glycolysis.

HEADING AIMS: LncRNA HOXB-AS3 is proved as an oncogene in tumors. Herein, we determine the function and mechanism of HOXB-AS3 in epithelial ovarian cancer (EOC) cells. MATERIALS AND METHODS: Chi-square test, Kaplan-Meier (KM) analysis and Cox regression analysis were used to analyze the clinicopathological features of HOXB-AS3 in EOC patients. CCK8, transwell and wound healing assay were used to test the function of HOXB-AS3. Luciferase reporter assay, western blot and glycolysis rate assay were used for further mechanistic studies. KEY FINDINGS: HOXB-AS3 was abundantly expressed in EOC tissues, and higher levels of HOXB-AS3 in EOC patients were significantly associated with disease status and overall survival status. EOC patients with high levels of HOXB-AS3 had strikingly shorter disease-free survival (DFS) and overall survival (OS) times than those with low levels. HOXB-AS3 also might as an independent prognostic factor. Further study revealed knockdown of HOXB-AS3 significantly inhibited the proliferation, invasion and migration of EOC cells. Mechanistic investigations suggested that knockdown of HOXB-AS3 could decrease lactate dehydrogenase A (LDHA) expression and the extracellular acidification rate (ECAR) by sponging miR-378a-3p. SIGNIFICANCE: To our knowledge, this is the first study to suggest that HOXB-AS3 could crosstalk with miRNA in the cytoplasm and alter glycolysis in cancer cells. Our results improve our understanding of the mechanism of HOXB-AS3 and suggest that HOXB-AS3 can act as a predictor of OS and a target for EOC therapies.

Risk Factors for Postpartum Stress Urinary Incontinence: a Systematic Review and Meta-analysis.

Stress urinary incontinence (SUI) is a distressing symptom affecting females globally and is one of the most common complications of delivery. The etiology of female SUI is multifactorial, and the trauma caused by delivery is one of the most important risk factors for SUI. We performed a meta-analysis to determine the relationship between these various factors and postpartum SUI. We searched PubMed, Embase, Web of Science, and the Cochrane Library until January 2019 using appropriate keywords and extracted 46 eligible studies that included 73,010 participants. The study protocol was registered with PROSPERO (No. CRD42020150094). The pooled results indicated that 12 risk factors, including vaginal delivery (OR 2.08, 95% CI 1.72-2.52), advanced age at gestation (OR 1.06, 95% CI 1.04-1.08), advanced maternal BMI (OR 1.04, 95% CI 1.03-1.06), excess weight gain during pregnancy (OR 1.13, 95% CI 1.00-1.26), advanced current BMI (OR 1.32, 95% CI 1.02-1.70), diabetes (OR 1.91, 95% CI 1.53-2.38), episiotomy (OR 1.76, 95% CI 1.06-2.94), forceps delivery (OR 2.69, 95% CI 1.25-5.76), gestational UI (OR 5.04, 95% CI 2.07-12.28), gestational SUI (OR 4.28, 95% CI 2.61-7.01), prenatal UI (OR 8.54, 95% CI 3.52-20.70), and early postpartum UI (OR 3.52, 95% CI 1.61-7.69), were associated with postpartum SUI. The findings of this analysis could serve to generate risk prediction models and provide a basis for developing treatment strategies for patients with postpartum SUI.

Microarray analysis reveals differentially expressed lncRNAs in benign epithelial ovarian cysts and normal ovaries.

Recent studies suggest that long non-coding RNAs (lncRNAs) play crucial roles in many types of human malignant cancers. However, the function of lncRNAs in benign tumors remains poorly understood. In the present study, to explored the potential roles of lncRNAs in benign epithelial ovarian cysts (BEOCs) which commonly occur in young women and possess malignant potential, we described the expression profile of the lncRNAs between BEOC and normal ovarian tissues using lncRNA microarray techniques. The results showed that 1,325 transcripts of lncRNAs (1,014 upregulated and 311 downregulated) were differentially expressed in the BEOCs compared with the normal controls [absolute fold-change ≥2, false discovery rate (FDR) <0.05]. We also conducted quantitative real-time PCR (qPCR) to confirm the microarray data. The results of qPCR revealed that the expression trend of 6 randomly selected lncRNAs was consistent with the microarray data. Furthermore, candidate lncRNAs were characterized by pathway analysis and Gene Ontology (GO). The present study is the first to demonstrate different expression profiles of lncRNAs between BEOCs and normal ovarian tissues. These lncRNAs may play a crucial role in the pathological process of BEOCs.

LncRNAs expression profiling in normal ovary, benign ovarian cyst and malignant epithelial ovarian cancer.

Long noncoding RNA (lncRNA) has been recognized as a regulator of gene expression, and the dysregulation of lncRNAs is involved in the progression of many types of cancer, including epithelial ovarian cancer (EOC). To explore the potential roles of lncRNAs in EOC, we performed lncRNA and mRNA microarray profiling in malignant EOC, benign ovarian cyst and healthy control tissues. In this study, 663 transcripts of lncRNAs were found to be differentially expressed in malignant EOC compared with benign and normal control tissues. We also selected 18 altered lncRNAs to confirm the validity of the microarray analysis using quantitative real-time PCR (qPCR). Pathway and Gene Ontology (GO) analyses demonstrated that these altered transcripts were involved in multiple biological processes, especially the cell cycle. Furthermore, Series Test of Cluster (STC) and lncRNA-mRNA co-expression network analyses were conducted to predict lncRNA expression trends and the potential target genes of lncRNAs. We also determined that two antisense lncRNAs (RP11-597D13.9 and ADAMTS9-AS1) were associated with their nearby coding genes (FAM198B, ADAMTS9), which participated in cancer progression. This study offers helpful information to understand the initiation and development mechanisms of EOC.

Trends of childhood obesity in China and associated factors.

Childhood obesity is worsening at dramatic rates and has become a public health crisis. This study investigated these trends in childhood obesity and examined parental factors that may contribute to overweight and obesity. Body mass index (BMI) was calculated from height and weight measurements taken annually from 2004 to 2007 in a subsample of 136 children (2-4 years old), from the Jintan Child Health Project in China. Parental factors were assessed through a self-administered questionnaire. Prevalence rates of overweight and obesity rose from 6.6% and 2.2% in 2004 to 15.4% and 6.6% in 2007 (p < .05). Overweight was significantly associated with maternal employment (p < .05), but not with parental education level, maternal age at birth, or breast-feeding. To counter this rapid increase of obesity and overweight prevalence, nurses should regularly monitor children's weight and advise parents, especially working mothers, on the nutritional benefits of home-cooked meals.