Metabolomics variation profiling of vaginal discharge identifies potential targets for cervical cancer early warning.
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ABSTRACT:
SUBMITTER: Xu H
PROVIDER: S-EPMC9827803 | biostudies-literature | 2022 Sep
REPOSITORIES: biostudies-literature
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Metabolomics variation profiling of vaginal discharge identifies potential targets for cervical cancer early warning.
Xu Hanjie H Liu Min M Song Yuexiao Y Liu Lou L Xu Feng F Chen Jiale J Zhan Huiying H Zhang Ye Y Chen Yu Y Lu Mudan M Chen Daozhen D
Acta biochimica et biophysica Sinica 20220901 10
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Project description:Bovine vaginal discharge Raw sequence reads
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Project description:BackgroundTo explore the role of vaginal microbiota and metabolomics in the progression of cervical dysplasia.MethodsThe patient group consists of female patients with low-grade, high-grade cervical dysplasia, and cervical cancer. Normal cervix samples from health volunteers were used as controls. The metabolic fingerprints of cervicovaginal lavage were analyzed using liquid chromatography-mass spectrometry, while the vaginal microbiota was examined through 16S rRNA sequencing. Bioinformatic analysis was adopted to investigate the interplay between hosts and microbes. The vaginal metabolic and microbiota profiles of 90 female patients with cervical dysplasia and 10 controls were analyzed to discover the biological characteristics underlying the progression of cervical cancer.ResultsWe found that Valyl-Glutamate, N, N'-Diacetylbenzidine, and Oxidized glutathione, which were involved in oxidative stress response, were discriminators to distinguish the normal cervix, invasive cervical carcinomas, and CIN3 from others. Cervical carcinoma was characterized by a large variety of vaginal microbes (dominated by non-Lactobacillus communities) compared to the control. These microbes affected amino acid and nucleotide metabolism, producing metabolites with cervical carcinoma and genital inflammation compared to the control group.ConclusionsThis study revealed that cervicovaginal metabolic profiles were determined by cervical cancer, vaginal microbiota, and their interplays. ROS metabolism can be used to discriminate normal cervix, CIN3, and invasive cervical carcinoma.
| S-EPMC11260971 | biostudies-literature
Project description:BackgroundCervical cancer (CC) is a danger to women's health, especially in many developing countries. Metabolomics can make the connection between genotypes and phenotypes. It provides a wide spectrum profile of biological processes under pathological or physiological conditions.MethodIn this study, we conducted plasma metabolomics of healthy volunteers and CC patients and integratively analyzed them with public CC tissue transcriptomics from Gene Expression Omnibus (GEO).ResultHere, we screened out a panel of 5 metabolites to precisely distinguish CC patients from healthy volunteers. Furthermore, we utilized multi-omics approaches to explore patients with stage I-IIA1 and IIA2-IV4 CC and comprehensively analyzed the dysregulation of genes and metabolites in CC progression. We identified that plasma levels of trimethylamine N-oxide (TMAO) were associated with tumor size and regarded as a risk factor for CC. Moreover, we demonstrated that TMAO could promote HeLa cell proliferation in vitro. In this study, we delineated metabolic profiling in healthy volunteers and CC patients and revealed that TMAO was a potential biomarker to discriminate between I-IIA1 and IIA2-IV patients to indicate CC deterioration.ConclusionOur study identified a diagnostic model consisting of five metabolites in plasma that can effectively distinguish CC from healthy volunteers. Furthermore, we proposed that TMAO was associated with CC progression and might serve as a potential non-invasive biomarker to predict CC substage.ImpactThese findings provided evidence of the important role of metabolic molecules in the progression of cervical cancer disease, as well as their ability as potential biomarkers.
| S-EPMC10980666 | biostudies-literature
Project description:BackgroundIn western Kenya, women often present with late-stage cervical cancer despite prior contact with the health care system. The aim of this study was to predict primary health care providers' behaviour in examining women who present with abnormal discharge or bleeding.MethodsThis was a cross-sectional survey using the theory of planned behaviour (TPB). A sample of primary health care practitioners in western Kenya completed a 59-item questionnaire. Structural equation modelling was used to identify the determinants of providers' intention to perform a gynaecological examination. Bivariate analysis was conducted to investigate the relationship between the external variables and intention.ResultsDirect measures of subjective norms (DMSN), direct measures of perceived behavioural control (DMPBC), and indirect measures of attitude predicted the intention to examine patients. Negative attitudes toward examining women had a suppressor effect on the prediction of health workers' intentions. However, the predictors of intention with the highest coefficients were the external variables being a nurse (β = 0.32) as opposed to a clinical officer and workload of attending less than 50 patients per day (β = 0.56). In bivariate analysis with intention to perform a gynaecological examination, there was no evidence that working experience, being female, having a lower workload, or being a private practitioner were associated with a higher intention to conduct vaginal examinations. Clinical officers and nurses were equally likely to examine women.ConclusionsThe TPB is a suitable theoretical basis to predict the intention to perform a gynaecological examination. Overall, the model predicted 47% of the variation in health care providers' intention to examine women who present with recurrent vaginal bleeding or discharge. Direct subjective norms (health provider's conformity with what their colleagues do or expect them to do), PBC (providers need to feel competent and confident in performing examinations in women), and negative attitudes toward conducting vaginal examination accounted for the most variance. External variables in this study also contributed to the overall variance. As the model in this study could not explain 53% of the variance, investigating other external variables that influence the intention to examine women should be undertaken.
| S-EPMC7953728 | biostudies-literature
Project description:BackgroundThis review aimed to synthesize and analyze the diagnostic accuracy and the likelihood of providing correct treatment of the syndromic approach Vaginal Discharge Flowchart in managing cervical infections caused by Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT), and vaginal infections caused by Trichomonas vaginalis (TV) and Bacterial vaginosis (BV) and Candida albicans. This review will inform updating the WHO 2003 guidelines on Vaginal Discharge syndromic case management.MethodsA systematic review was conducted on published studies from 01-01-2000 to 30-03-2015 in multiple databases. Studies evaluating the diagnostic accuracy and validation of the WHO Vaginal Discharge Flowchart were included. Validation parameters including sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) and the 95% confidence intervals for the different types of the flowchart were taken as outcomes, re-calculated, and analysed using a fixed model meta-analysis for data pooling. The level of agreement between the index and reference test were determined by the Cohen's Kappa co-efficiency test. Each individual study was assessed on quality using the QUADAS-2 tool.FindingsThe search yielded 2,845 studies of which 16 met the eligibility criteria for final analysis. The diagnostic performance to identify cervical infections was low and resulted in a high proportion of over and missed treatment. The four flowcharts had a sensitivity between 27.37% in history and risk assessment and 90.13% with microscopy, with the inverse in specificity rates. The treatment performances between the flowcharts were inconsistent. The same applies to the use of vaginal discharge flowchart for treating vaginal infections. For vaginal infections the vaginal discharge flowchart had a good performance in flowchart 3 with 91.68% of sensitivity; 99.97% specificity; 99.93% PPV and 0.02% who missed their treatment and 8.32% of women who were over treated by the vaginal discharge flowchart.ConclusionThe vaginal discharge flowchart should focus on management of vaginal infection. It could be used as an intermediate approach for cervical infections for sex workers until a point of care test is available in resource poor settings.
| S-EPMC5052075 | biostudies-literature
Project description:Background: Vaginal discharge is a common clinical problem with varied etiologies, most common being bacterial vaginosis which presents as homogenous gray discharge caused by overgrowth of facultative and anaerobic bacterial species, next common is vulvovaginal candidiasis characterized by pruritus and cottage cheese like discharge followed by vaginal trichomoniasis associated with copious yellow or green and frothy discharge. This necessitates the need to identify the specific cause of vaginal discharge. Aim: To determine the etiology of pathological vaginal discharges in women attending tertiary care hospital. Methodology: 698 sexually active females in age group of 15 to 65 years with complaints of vaginal discharge attending Department of Dermatology Venereology and Leprosy at a Tertiary care hospital from June 2017 to May 2018 participated in the study. After presumptive clinical diagnosis vaginal discharge was collected. Wet mounts and 10% KOH preparations were examined immediately. Identification of pathogens was done by Gram stain and culture. Results: 18.33% of 698 patients showed vulvovaginal candidiasis, 13.75% had bacterial vaginosis, 1.86% showed trichomoniasis. Gold standard was considered to be culture for candidiasis & trichomoniasis whereas for bacterial vaginosis it was Nugent's score. Conclusions: Vaginal discharge is of multiple yet specific etiologies hence simple and minimal tests like microscopy available in most laboratories (supported by culture wherever possible) would help in accurate diagnosis without over or under treatment of patient due to the empirical therapy. Syndromic management of STIs (WHO guidelines) should be used only in non-specific cases.
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Project description:Although there has been significant progress in prevention and treatment of cervical cancer, this malignancy is still a leading cause of cancer death for women. Anti-angiogenesis and immunotherapy approaches have been providing survival benefits, however, response rates and durability of response need to be improved. There is a clear need for combination therapies that increase effectiveness of these agents and further improve patient outcome. Previous studies have largely focused on gene expression and molecular pathways in untreated cervix cancer. The goal of this study was to evaluate cancer-specific molecular pathways and their correlation with tumor immune profile in recurrent cervical cancer. Tumor and adjacent normal tissues were used to identify potential combination therapy targets. We found that DNA damage repair pathway genes were significantly overexpressed in the tumor. Based on our results and other recent investigations, we suggest that combination immune checkpoint and PARP inhibitor therapy is a high priority consideration for patients with recurrent, previously treated cervical cancer. We also show that multiple epithelial-mesenchymal transition-related genes, including MAP2K4, ID2, JAK1, FGF2, PIK3R1, AKT3, FGF13, and STAT3 may be potential targets. Interestingly, high-throughput analysis of Cancer Genome Atlas data identified distinct targets, including Fatty acid synthase FASN and Matrix Metallopeptidase 1 MMP1 as novel, promising combination therapy partners.
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Project description:We collected vaginal discharge from 30 ovarian cancer patients and 29 benign gynecological disease patients, extracted exosomal miRNAs, and examined the expression differences between groups by RT-qPCR.
2025-05-07 | GSE271256 | GEO
Project description:Despite advances in management, bladder cancer remains a major cause of cancer related complications. Characterisation of gene expression patterns in bladder cancer allows the identification of pathways involved in its pathogenesis, and may stimulate the development of novel therapies targeting these pathways. Between 2004 and 2005, cystoscopic bladder biopsies were obtained from 19 patients and 11 controls. These were subjected to whole transcript-based microarray analysis. Unsupervised hierarchical clustering was used to identify samples with similar expression profiles. Hypergeometric analysis was used to identify canonical pathways and curated networks having statistically significant enrichment of differentially expressed genes. Osteopontin (OPN) expression was validated by immunohistochemistry. Hierarchical clustering defined signatures, which differentiated between cancer and healthy tissue, muscle-invasive or non-muscle invasive cancer and healthy tissue, grade 1 and grade 3. Pathways associated with cell cycle and proliferation were markedly upregulated in muscle-invasive and grade 3 cancers. Genes associated with the classical complement pathway were downregulated in non-muscle invasive cancer. Osteopontin was markedly overexpressed in invasive cancer compared to healthy tissue. The present study contributes to a growing body of work on gene expression signatures in bladder cancer. The data support an important role for osteopontin in bladder cancer, and identify several pathways worthy of further investigation.
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