Proteomics approach to discovering non-invasive diagnostic biomarkers and understanding the pathogenesis of endometriosis: a systematic review and meta-analysis.

BACKGROUND: Endometriosis is one of the most common gynaecological diseases, yet it lacks efficient biomarkers for early detection and unravels disease mechanisms. Proteomic profiling has revealed diverse patterns of protein changes in various clinical samples. Integrating and systematically analysing proteomics data can facilitate the development of biomarkers, expediting diagnosis and providing insights for potential clinical and therapeutic applications. Hence, this systematic review and meta-analysis aimed to explore potential non-invasive diagnostic biomarkers in various biological samples and therapeutic targets for endometriosis. METHODS: Online databases, including Scopus, PubMed, Web of Science, MEDLINE, Embase via Ovid, and Google Scholar, were searched using MeSH terms. Two independent authors screened the articles, extracted the data, and assessed the methodological quality of the included studies. GO and KEGG analyses were performed to identify the pathways that were significantly enriched. Protein­protein interaction and hub gene selection analyses were also conducted to identify biomarker networks for endometriosis. RESULTS: Twenty-six observational studies with a total of 2,486 participants were included. A total of 644 differentially expressed proteins (180 upregulated and 464 downregulated) were identified from 9 studies. Proteins in peripheral blood exhibited a sensitivity and specificity of 38-100% and 59-99%, respectively, for detecting endometriosis, while proteins in urine had a sensitivity of 58-91% and specificity of 76-93%. Alpha-1-antitrypsin, albumin, and vitamin D binding proteins were significantly DEPs in both serum and urine. Complement C3 is commonly expressed in serum, menstrual blood, and cervical mucus. Additionally, S100-A8 is commonly expressed in both menstrual blood and cervical mucus. Haptoglobin is commonly detected in both serum and plasma, whereas cathepsin G is found in urine, serum, and plasma. GO and KEGG enrichment analyses revealed that proteoglycans in cancer pathways, which regulate cell-to-cell interactions, modulate the extracellular matrix, and promote the proliferation and invasion of endometrial cells, are commonly enriched in serum and urine. CONCLUSION: This comprehensive study revealed potential proteomes that were significantly differentially expressed in women with endometriosis utilizing various non-invasive clinical samples. Exploring common differentially expressed proteins in various biological samples provides insights into the diagnosis and pathophysiology of endometriosis, as well as potential clinical and therapeutic applications.

Therapeutic effects of green tea on endometriosis.

Endometriosis is a chronic disorder characterized by the presence of endometrial glands and stroma outside the uterine cavity. It affects 8%-10% of women in their reproductive years, and represents a major clinical problem with deleterious social, sexual and reproductive consequences. Current treatment options include pain relief, hormonal intervention and surgical removal. However, these treatments are deemed unsatisfactory owing to varying success, significant side effects and high recurrence rates. Green tea and its major bioactive component, (-)-epigallocatechin gallate (EGCG), possess diverse biological properties, particularly anti-angiogenic, anti-proliferation, anti-metastasis, and apoptosis induction. In recent years, preclinical studies have proposed the use of green tea to inhibit the growth of endometriosis. Herein, the aim of this review is to summarize the potential therapeutic effects of green tea on molecular and cellular mechanism through inflammation, oxidative stress, invasion and adhesion, apoptosis and angiogenesis in endometriosis.

Oxytocin-Augmented and Non-Sedating High-Intensity-Focused Ultrasound (HIFU) for Uterine Fibroids Showed Promising Outcome As Compared To HIFU Alone or Uterine Artery Embolization.

The use of a modified energy transmission protocol and oxytocin augmentation is being proposed as a high-intensity-focused ultrasound (HIFU) treatment for uterine fibroids, to aim for an effective and well-tolerable treatment to be given as an out-patient procedure without anesthesia or sedation. The objective of this study was to evaluate the safety and treatment effectiveness of this new protocol. The treatment outcomes of 9 consecutive patients (study group) were compared with those of 51 patients (control group) who had been randomized (1:1) to receive HIFU (n = 24) or uterine artery embolization ([UAE] n = 27). There was no major adverse event. At 3 mo, the median proportion of fibroid volume compared with the baseline was 51.1% in the study group, significantly smaller than that in the control groups (HIFU 76.6%, UAE 66.2%). At 6 mo, all patients in the study group became symptom free (9/9, 100%), a result significantly better than that of both control groups. The proportion of patients with good quality of life was significantly higher in the study group (5/7, 71.4%) compared with the control groups (HIFU 3/24, 12.5%; UAE 7/27, 25.9%). Within 24 mo, none of the patients in the study HIFU group required re-intervention, a result significantly better than that in the control HIFU group (15/24, 62.5%). The treatment could result in a very promising long-term imaging and clinical outcome that may be better than those of UAE; however, a randomized control trial of larger scale is required for further evaluation of this treatment.

Development and validation of prediction models for endometrial cancer in postmenopausal bleeding.

OBJECTIVE: To develop and assess the accuracy of risk prediction models to diagnose endometrial cancer in women having postmenopausal bleeding (PMB). METHODS: A retrospective cohort study of 4383 women in a One-stop PMB clinic from a university teaching hospital in Hong Kong. Clinical risk factors, transvaginal ultrasonic measurement of endometrial thickness (ET) and endometrial histology were obtained from consecutive women between 2002 and 2013. Two models to predict risk of endometrial cancer were developed and assessed, one based on patient characteristics alone and a second incorporated ET with patient characteristics. Endometrial histology was used as the reference standard. The split-sample internal validation and bootstrapping technique were adopted. The optimal threshold for prediction of endometrial cancer by the final models was determined using a receiver-operating characteristics (ROC) curve and Youden Index. The diagnostic gain was compared to a reference strategy of measuring ET only by comparing the AUC using the Delong test. RESULTS: Out of 4383 women with PMB, 168 (3.8%) were diagnosed with endometrial cancer. ET alone had an area under curve (AUC) of 0.92 (95% confidence intervals [CIs] 0.89-0.94). In the patient characteristics only model, independent predictors of cancer were age at presentation, age at menopause, body mass index, nulliparity and recurrent vaginal bleeding. The AUC and Youdens Index of the patient characteristic only model were respectively 0.73 (95% CI 0.67-0.80) and 0.72 (Sensitivity=66.5%; Specificity=68.9%; +ve LR=2.14; -ve LR=0.49). ET, age at presentation, nulliparity and recurrent vaginal bleeding were independent predictors in the patient characteristics plus ET model. The AUC and Youdens Index of the patient characteristic plus ET model where respectively 0.92 (95% CI 0.88-0.96) and 0.71 (Sensitivity=82.7%; Specificity=88.3%; +ve LR=6.38; -ve LR=0.2). Comparison of AUC indicated that a history alone model was inferior to a model using ET alone (difference=0.19, 95% CI 0.15-0.24; p<0.0001) and History plus ET (difference=0.19, 95% CI 0.16-0.23, p<0.0001) and history plus ET was similar to that of using ET alone (difference=0.001 95% CI -0.015 to 0.0018, p=0.84). CONCLUSIONS: A risk model using only patient characteristics showed fair diagnostic accuracy. Addition of patient characteristics to ET did not improve the diagnostic accuracy as compared to ET alone in our cohort.

Seroprevalence of varicella zoster virus among pregnant women in Hong Kong: comparison with self-reported history.

OBJECTIVE: To compare seroprevalence (serum IgG titre) with self-reported history of varicella zoster virus (VZV) infection among pregnant women in Hong Kong. METHODS: Pregnant women undergoing first trimester Down screening over a 3-months period were recruited for the study. RESULTS: Positive immunity was found in 477 (95.4%) of the 500 recruited women, and those with positive, negative, or uncertain history of infection had similarly high seroprevalence (96.4, 90.5, 95.9% respectively). The mean age of infection from self-recalled history was 8.61 (SD 4.69) years, and only 3% recalled infection after age 18. Insufficient knowledge on the disease and vaccination was demonstrated. CONCLUSIONS: Despite the absence of a routine vaccination programme, VZV immunity was high among pregnant women, the majority being infected during childhood and infection above age 18 was very rare. Hence, universal antenatal screening or vaccination for all women in the reproductive age would not be cost-effective in Hong Kong.