scholarly journals A pilot study of discovery and validation of peritoneal endometriosis biomarkers in peritoneal fluid and serum

2020 ◽  
Author(s):  
See Ling Loy ◽  
Jieliang Zhou ◽  
Liang Cui ◽  
Tse Yeun Tan ◽  
Tat Xin Ee ◽  
...  
Keyword(s):  
Peritoneal Fluid ◽  
Liquid Chromatography Mass Spectrometry ◽  
Operating Characteristics ◽  
Targeted Metabolomics ◽  
Serum Samples ◽  
Pilot Studies ◽  
Potential Biomarker ◽  
Receiver Operating Characteristics Curve ◽  
Peritoneal Endometriosis ◽  
Validation Set

ObjectiveTo identify potential serum biomarkers in women with peritoneal endometriosis (PE) by first looking at its source in the peritoneal fluid (PF).DesignCase-control pilot studies, comprising independent discovery and validation sets.SettingKK Women’s and Children’s Hospital, Singapore.Patient(s)Women with laparoscopically confirmed PE and absence of endometriosis (control).Intervention(s)None.Main Outcome Measure(s)In the discovery set, we used untargeted liquid chromatography-mass spectrometry (LC-MS/MS) metabolomics, multivariable and univariable analyses to generate global metabolomic profiles of PF for endometriosis and to identify potential metabolites that could distinguish PE (n=10) from controls (n=31). Using targeted metabolomics, we validated the identified metabolites in PF and sera of cases (n=16 PE) and controls (n=19). We performed the area under the receiver-operating characteristics curve (AUC) analysis to evaluate the diagnostic performance of PE metabolites.Result(s)In the discovery set, PF phosphatidylcholine (34:3) and phenylalanyl-isoleucine were significantly increased in PE than controls groups, with AUC 0.77 (95% confidence interval 0.61-0.92; p=0.018) and AUC 0.98 (0.95-1.02; p<0.001), respectively. In the validation set, phenylalanyl-isoleucine retained discriminatory performance to distinguish PE from controls in both PF (AUC 0.77; 0.61-0.92; p=0.006) and serum samples (AUC 0.81; 0.64-0.99; p=0.004).Conclusion(s)Our preliminary results propose phenylalanyl-isoleucine as a potential biomarker of PE, which may be used as a minimally-invasive diagnostic biomarker of PE.

scholarly journals A non-targeted LC–MS metabolic profiling of pregnancy: longitudinal evidence from healthy and pre-eclamptic pregnancies

Metabolomics ◽  
2021 ◽  
Vol 17 (2) ◽  
Author(s):  
Tiina Jääskeläinen ◽  
◽  
Olli Kärkkäinen ◽  
Jenna Jokkala ◽  
Anton Klåvus ◽  
...  
Keyword(s):  
Large Scale ◽  
Scale Effects ◽  
Late Pregnancy ◽  
Metabolite Profile ◽  
Adverse Outcomes ◽  
Liquid Chromatography Mass Spectrometry ◽  
Targeted Metabolomics ◽  
Serum Samples ◽  
Healthy Women ◽  
Maternal Metabolism

Abstract Introduction Maternal metabolism changes substantially during pregnancy. However, few studies have used metabolomics technologies to characterize changes across gestation. Objectives and methods We applied liquid chromatography–mass spectrometry (LC–MS) based non-targeted metabolomics to determine whether the metabolic profile of serum differs throughout the pregnancy between pre-eclamptic and healthy women in the FINNPEC (Finnish Genetics of Preeclampsia Consortium) Study. Serum samples were available from early and late pregnancy. Results Progression of pregnancy had large-scale effects to the serum metabolite profile. Altogether 50 identified metabolites increased and 49 metabolites decreased when samples of early pregnancy were compared to samples of late pregnancy. The metabolic signatures of pregnancy were largely shared in pre-eclamptic and healthy women, only urea, monoacylglyceride 18:1 and glycerophosphocholine were identified to be increased in the pre-eclamptic women when compared to healthy controls. Conclusions Our study highlights the need of large-scale longitudinal metabolomic studies in non-complicated pregnancies before more detailed understanding of metabolism in adverse outcomes could be provided. Our findings are one of the first steps for a broader metabolic understanding of the physiological changes caused by pregnancy per se.

scholarly journals Untargeted Metabolomics and Polyamine Profiling in Serum before and after Surgery in Colorectal Cancer Patients

Metabolites ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 487
Author(s):  
Yu Ra Lee ◽  
Ki-Yong An ◽  
Justin Jeon ◽  
Nam Kyu Kim ◽  
Ji Won Lee ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metabolic Pathways ◽  
Sphingolipid Metabolism ◽  
Proline Metabolism ◽  
Liquid Chromatography Mass Spectrometry ◽  
Targeted Metabolomics ◽  
Serum Samples ◽  
Physiological Alterations ◽  
Before And After ◽  
Colorectal Cancer Patients

Colorectal cancer is one of the most prevalent cancers in Korea and globally. In this study, we aimed to characterize the differential serum metabolomic profiles between pre-operative and post-operative patients with colorectal cancer. To investigate the significant metabolites and metabolic pathways associated with colorectal cancer, we analyzed serum samples from 68 patients (aged 20–71, mean 57.57 years). Untargeted and targeted metabolomics profiling in patients with colorectal cancer were performed using liquid chromatography-mass spectrometry. Untargeted analysis identified differences in sphingolipid metabolism, steroid biosynthesis, and arginine and proline metabolism in pre- and post-operative patients with colorectal cancer. We then performed quantitative target profiling of polyamines, synthesized from arginine and proline metabolism, to identify potential polyamines that may serve as effective biomarkers for colorectal cancer. Results indicate a significantly reduced serum concentration of putrescine in post-operative patients compared to pre-operative patients. Our metabolomics approach provided insights into the physiological alterations in patients with colorectal cancer after surgery.

scholarly journals Sphingolipid Analysis Indicate Lactosylceramide as a Potential Biomarker of Inflammatory Bowel Disease in Children

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1083
Author(s):  
Aleksandra Filimoniuk ◽  
Agnieszka Blachnio-Zabielska ◽  
Monika Imierska ◽  
Dariusz Marek Lebensztejn ◽  
Urszula Daniluk
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
High Performance ◽  
Area Under The Curve ◽  
Study Groups ◽  
Diagnostic Value ◽  
Serum Samples ◽  
Specificity And Sensitivity ◽  
Potential Biomarker ◽  
Inflammatory Bowel

An altered ceramide composition in patients with inflammatory bowel disease (IBD) has been reported recently. The aim of this study was to evaluate the concentrations of sphingolipids in the serum of treatment-naive children with newly diagnosed IBD and to determine the diagnostic value of the tested lipids in pediatric IBD. The concentrations of sphingolipids in serum samples were evaluated using a quantitative method, an ultra-high-performance liquid chromatography-tandem mass spectrometry in children with Crohn’s disease (CD) (n=34), ulcerative colitis (UC) (n = 39), and controls (Ctr) (n = 24). Among the study groups, the most significant differences in concentrations were noted for C16:0-LacCer, especially in children with CD compared to Ctr or even to UC. Additionally, the relevant increase in C20:0-Cer and C18:1-Cer concentrations were detected in both IBD groups compared to Ctr. The enhanced C24:0-Cer level was observed only in UC, while C18:0-Cer only in the CD group. The highest area under the curve (AUC), specificity, and sensitivity were determined for C16:0-LacCer in CD diagnosis. Our results suggest that the serum LacC16-Cer may be a potential biomarker that distinguishes children with IBD from healthy controls and differentiates IBD subtypes. In addition, C20:0-Cer and C18:0-Cer levels also seem to be closely connected with IBD.

scholarly journals Dysregulations of MicroRNA and Gene Expression in Chronic Venous Disease

2020 ◽  
Vol 9 (5) ◽  
pp. 1251 ◽  
Author(s):  
Daniel P. Zalewski ◽  
Karol P. Ruszel ◽  
Andrzej Stępniewski ◽  
Dariusz Gałkowski ◽  
Jacek Bogucki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mononuclear Cells ◽  
Varicose Veins ◽  
Expression Profiles ◽  
Lower Limbs ◽  
Chronic Venous Disease ◽  
Venous Disease ◽  
Operating Characteristics ◽  
Potential Biomarker ◽  
Pathologic Features

Chronic venous disease (CVD) is a vascular disease of lower limbs with high prevalence worldwide. Pathologic features include varicose veins, venous valves dysfunction and skin ulceration resulting from dysfunction of cell proliferation, apoptosis and angiogenesis. These processes are partly regulated by microRNA (miRNA)-dependent modulation of gene expression, pointing to miRNA as a potentially important target in diagnosis and therapy of CVD progression. The aim of the study was to analyze alterations of miRNA and gene expression in CVD, as well as to identify miRNA-mediated changes in gene expression and their potential link to CVD development. Using next generation sequencing, miRNA and gene expression profiles in peripheral blood mononuclear cells of subjects with CVD in relation to healthy controls were studied. Thirty-one miRNAs and 62 genes were recognized as potential biomarkers of CVD using DESeq2, Uninformative Variable Elimination by Partial Least Squares (UVE-PLS) and ROC (Receiver Operating Characteristics) methods. Regulatory interactions between potential biomarker miRNAs and genes were projected. Functional analysis of microRNA-regulated genes revealed terms closely related to cardiovascular diseases and risk factors. The study shed new light on miRNA-dependent regulatory mechanisms involved in the pathology of CVD. MicroRNAs and genes proposed as CVD biomarkers may be used to develop new diagnostic and therapeutic methods.

scholarly journals UHPLC-ESI-MS/MS Quantification of Relevant Substrates and Metabolites of the Kynurenine Pathway Present in Serum and Peritoneal Fluid from Gastric Cancer Patients—Method Development and Validation

2021 ◽  
Vol 22 (13) ◽  
pp. 6972
Author(s):  
Ilona Sadok ◽  
Katarzyna Jędruchniewicz ◽  
Karol Rawicz-Pruszyński ◽  
Magdalena Staniszewska
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Peritoneal Fluid ◽  
Method Development ◽  
Solid Phase ◽  
Kynurenine Pathway ◽  
Serum Samples ◽  
Esi Ms ◽  
Gastric Cancer Patients ◽  
Development And Validation

Metabolites and enzymes involved in the kynurenine pathway (KP) are highly promising targets for cancer treatment, including gastrointestinal tract diseases. Thus, accurate quantification of these compounds in body fluids becomes increasingly important. The aim of this study was the development and validation of the UHPLC-ESI-MS/MS methods for targeted quantification of biologically important KP substrates (tryptophan and nicotinamide) and metabolites(kynurenines) in samples of serum and peritoneal fluid from gastric cancer patients. The serum samples were simply pretreated with trichloroacetic acid to precipitate proteins. The peritoneal fluid was purified by solid-phase extraction before analysis. Validation was carried out for both matrices independently. Analysis of the samples from gastric cancer patients showed different accumulations of tryptophan and its metabolites in different biofluids of the same patient. The protocols will be used for the evaluation of tryptophan and kynurenines in blood and peritoneal fluid to determine correlation with the clinicopathological status of gastric cancer or the disease’s prognosis.

scholarly journals Etiological Work-Up for Adults with Bronchiectasis: A Predictive Diagnostic Score for Primary Ciliary Dyskinesia and Cystic Fibrosis

2021 ◽  
Vol 10 (16) ◽  
pp. 3478
Author(s):  
Frederic Schlemmer ◽  
Agnes Hamzaoui ◽  
Sonia Zebachi ◽  
Aurelie Le Thuaut ◽  
Gilles Mangiapan ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Primary Ciliary Dyskinesia ◽  
Clinical Score ◽  
Adult Patients ◽  
Operating Characteristics ◽  
Diagnostic Score ◽  
Receiver Operating Characteristics Curve ◽  
Diagnostic Work ◽  
Work Up ◽  
Ciliary Dyskinesia

Background: etiological investigations are not done for all adult patients with bronchiectasis because of the availability and interpretation of tests. The aim of the study was to elaborate a score to identify patients at high risk of having cystic fibrosis or primary ciliary dyskinesia (CF/PCD), which require appropriate management. Methods: diagnostic work-ups were carried out on a French monocenter cohort, and results were subjected to logistic-regression analyses to identify the independent factors associated with CF/PCD diagnosis and, thereby, elaborate a score to validate in a second cohort. Results: among 188 patients, 158 had no obvious diagnosis and were enrolled in the algorithm-construction group. In multivariate analyses, age at symptom onset (8.69 (2.10–35.99); p = 0.003), chronic ENT symptoms or diagnosed sinusitis (10.53 (1.26–87.57); p = 0.03), digestive symptoms or situs inversus (5.10 (1.23–21.14); p = 0.025), and Pseudomonas. aeruginosa and/or Staphylococcus aureus isolated from sputum (11.13 (1.34–92.21); p = 0.02) are associated with CF or PCD. Receiver operating characteristics curve analysis, using a validation group of 167 patients with bronchiectasis, confirmed the score’s performance with AUC 0.92 (95% CI: 0.84–0.98). Conclusions: a clinical score may help identify adult patients with bronchiectasis at higher risk of having CF or PCD.

scholarly journals A novel combination of serum microRNAs for the detection of early gastric cancer

2021 ◽  
Author(s):  
Seiichiro Abe ◽  
Juntaro Matsuzaki ◽  
Kazuki Sudo ◽  
Ichiro Oda ◽  
Hitoshi Katai ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Early Gastric Cancer ◽  
Expression Profiles ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Cancer Center ◽  
Serum Samples ◽  
Retrospective Case ◽  
Serum Mirnas ◽  
Validation Set

Abstract Background The aim of this study was to identify serum miRNAs that discriminate early gastric cancer (EGC) samples from non-cancer controls using a large cohort. Methods This retrospective case–control study included 1417 serum samples from patients with EGC (seen at the National Cancer Center Hospital in Tokyo between 2008 and 2012) and 1417 age- and gender-matched non-cancer controls. The samples were randomly assigned to discovery and validation sets and the miRNA expression profiles of whole serum samples were comprehensively evaluated using a highly sensitive DNA chip (3D-Gene®) designed to detect 2565 miRNA sequences. Diagnostic models were constructed using the levels of several miRNAs in the discovery set, and the diagnostic performance of the model was evaluated in the validation set. Results The discovery set consisted of 708 samples from EGC patients and 709 samples from non-cancer controls, and the validation set consisted of 709 samples from EGC patients and 708 samples from non-cancer controls. The diagnostic EGC index was constructed using four miRNAs (miR-4257, miR-6785-5p, miR-187-5p, and miR-5739). In the discovery set, a receiver operating characteristic curve analysis of the EGC index revealed that the area under the curve (AUC) was 0.996 with a sensitivity of 0.983 and a specificity of 0.977. In the validation set, the AUC for the EGC index was 0.998 with a sensitivity of 0.996 and a specificity of 0.953. Conclusions A novel combination of four serum miRNAs could be a useful non-invasive diagnostic biomarker to detect EGC with high accuracy. A multicenter prospective study is ongoing to confirm the present observations.

CPVA: a web-based metabolomic tool for chromatographic peak visualization and annotation

2020 ◽  
Vol 36 (12) ◽  
pp. 3913-3915
Author(s):  
Hemi Luan ◽  
Xingen Jiang ◽  
Fenfen Ji ◽  
Zhangzhang Lan ◽  
Zongwei Cai ◽  
...  
Keyword(s):  
False Positive ◽  
Supplementary Information ◽  
Liquid Chromatography Mass Spectrometry ◽  
Targeted Metabolomics ◽  
Metabolomics Data ◽  
Web Based ◽  
Tremendous Amount ◽  
Chromatographic Peaks ◽  
User Friendly

Abstract Motivation Liquid chromatography–mass spectrometry-based non-targeted metabolomics is routinely performed to qualitatively and quantitatively analyze a tremendous amount of metabolite signals in complex biological samples. However, false-positive peaks in the datasets are commonly detected as metabolite signals by using many popular software, resulting in non-reliable measurement. Results To reduce false-positive calling, we developed an interactive web tool, termed CPVA, for visualization and accurate annotation of the detected peaks in non-targeted metabolomics data. We used a chromatogram-centric strategy to unfold the characteristics of chromatographic peaks through visualization of peak morphology metrics, with additional functions to annotate adducts, isotopes and contaminants. CPVA is a free, user-friendly tool to help users to identify peak background noises and contaminants, resulting in decrease of false-positive or redundant peak calling, thereby improving the data quality of non-targeted metabolomics studies. Availability and implementation The CPVA is freely available at http://cpva.eastus.cloudapp.azure.com. Source code and installation instructions are available on GitHub: https://github.com/13479776/cpva. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Evaluating the Risk of Tumors Diseases Based on Measurement of Urinary and Serumal Antioxidants Using the New Agar Diffusion Methods

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Ying Zhou ◽  
Jing Chen ◽  
Zhen Wang ◽  
Hui Liu
Keyword(s):  
Antioxidant Capacity ◽  
Healthy People ◽  
Healthy Individuals ◽  
Operating Characteristics ◽  
Tumor Patients ◽  
Tumor Diseases ◽  
Receiver Operating Characteristics Curve ◽  
Age Range ◽  
Urine And Serum ◽  
Effect Of Age

Objectives. To discuss the characteristics of the amount of urinary total antioxidants in tumor diseases and the possibility of utilizing the changing regulation of urinary antioxidants to diagnose tumor diseases.Method. Urine and serum specimens from 130 healthy people were used to investigate the variation of antioxidant capacity against age. Urine and serum specimens from 44 unselected patients with tumors and 44 healthy people with same age background were used to explore the significance of urinary antioxidant capacity in clinic to diagnose tumor diseases. Potassium permanganate agar method and iodine starch method were used to determine the amount of total antioxidants.Results. In healthy people, more antioxidants in urine were measured in older people, while the results were opposite in serum. More antioxidants were found in urine of tumor patients than in healthy people with same age-range.Conclusions. According to the results of 130 measurements, the amount of antioxidants in urine varies by age. By using agar methods to measure antioxidants, the effect of age is required to be considered. Antioxidants levels from tumor patients were significantly higher than healthy individuals in urine. The combination of urine and serum to determine total antioxidants can better diagnose tumor diseases based on iodine starch method, with area under the receiver operating characteristics curve at 0.787.

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