Identification and validation of circulating miRNAs as potential new biomarkers for severe liver disease in patients with leptospirosis
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PROVIDER: PRJNA743674 | ENA |
REPOSITORIES: ENA
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Project description:Background: Leptospirosis, a global zoonotic infectious disease, has various clinical manifestations ranging from mild self-limiting illness to life-threatening with multi-organ damage, including liver involvement. This study was aimed at identifying circulating microRNAs (miRNAs) as novel biomarkers for predicting severe liver involvement in patients with leptospirosis. Methods: In a discovery set, 12 serum samples of patients with anicteric and icteric leptospirosis at initial clinical presentation were used for miRNA profiling by a NanoString nCounter miRNA assay. In a validated cohort, top candidate miRNAs were selected and further tested by qRT-PCR in serum samples of 81 and 16 individuals with anicteric and icteric leptospirosis, respectively. Results: The discovery set identified 38 significantly differential expression miRNAs between the two groups. Among these, miR-601 and miR-630 were selected as the top two candidates significantly up-regulated expressed in the icteric group. The enriched KEGG pathway showed that these miRNAs were mainly involved in immune responses and inflammation. In the validated cohort, miR-601 and miR-630 levels were significantly higher in the icteric group compared with the anicteric group. Additionally, these two miRNAs displayed good predictors of subsequent acute liver failure with a high sensitivity of 100%. On regression analysis, elevated miR-601 and miR-630 expression were also predictive of multi-organ failures and poor overall survival. Conclusion: Our data indicated that miRNA expression profiles were significantly differentiated between the icteric and anicteric groups. Serum miR-601 and miR-630 at presentation could potentially serve as promising biomarkers for predicting subsequent acute liver failure and overall survival in patients with leptospirosis.
2021-07-07 | GSE179426 | GEO
Project description:Background: Leptospirosis is a global zoonotic infectious disease with various clinical manifestations ranging from mild self-limiting illness to life-threatening infection with multi-organ damage. This study was aimed at investigating transcription profiles from whole blood samples of patients with leptospirosis and identifying genes as novel biomarkers for predicting severe leptospirosis. Methods: In a discovery cohort, 12 serum samples of patients with severe and non-severe leptospirosis at initial clinical presentation were selected for gene expression profiling using the NanoString nCounter PanCancer IO 360 gene expression panel. In a validated cohort of 99 samples, top candidate genes were selected and further tested by qRT-PCR in whole blood samples of 30 and 69 individuals with severe and non-severe leptospirosis, respectively. Results: The discovery set identified 20 differentially expressed genes (DEGs) among the two groups. The top three down-regulated candidate genes including programmed cell death 1 (PDCD1), interleukin 4 (IL4), and nitric oxide synthase 2 (NOS2) were selected and further validated. In the validated cohort, PDCD1 levels were significantly lower in the severe group compared with the non-severe group(Stats?). Based on the ROC analysis, PDCD1 levels could discriminate between the severe and non-severe groups. Additionally , PDCD1 levels displayed good predictive power of subsequent pulmonary hemorrhage with an AUROC of 0.86 (95% CI;0.76-0.96, p = 0.007). PDCD1 also emerged as an independent prognostic factor of severe leptospirosis in the multivariate regression analysis.. Conclusion: Our data indicated that whole blood gene expression profiles were significantly different between the severe and non-severe leptospirosis groups. PDCD1 expression levels at presentation could potentially serve as a biomarker for predicting severe leptospirosis.
2025-04-01 | GSE200188 | GEO
Project description:Leptospirosis is zoonotic disease of global importance, with over a million cases andnearly 60,000 deaths annually. Symptomatic disease presentation ranges from a mildfebrile disease with non-specific symptoms to severe forms, characterized by multi-organ failure, lung hemorrhage, and death. Factors governing severe outcomes remainunclear, but the host immune response likely plays an important role. In the presentstudy, we applied high throughput techniques to identify the antibody profiles ofpatients with severe and mild leptospirosis. We discovered a limited number ofimmunodominant antigens, specific to patients. Surprisingly, we found the antibodyrepertoire varies in patients with different clinical outcomes and hypothesized thatpatients with mild symptoms were protected from severe disease due to pre-existingantibodies, while the profile of patients with severe outcomes was representative of afirst exposure. These findings represent a substantial step forward in the knowledge ofthe humoral immune response to Leptospira infection, and we have identified newtargets for vaccine and diagnostic test development.
2016-09-10 | GSE86630 | GEO
Project description:MicroRNAs Biomarkers and Host Response Pathways in Severe Pulmonary Hemorrhagic Syndrome due to Leptospirosis
| PRJNA1195885 | ENA
Project description:Background: dengue is a potentially life-threatening viral infection. Early prognostic markers of severe complications may improve case management and reduce dengue-related mortalities. This study aimed to identify circulating microRNAs (miRNAs) as biomarkers for predicting severe dengue. Methods: Serum samples from dengue-infected patients were collected on the first day of admission. Patients were followed up for 14 days after admission to determine the final diagnosis. Participants were divided into non-severe and severe dengue, as defined by WHO 2009 criteria. Circulating microtranscriptome analysis was performed using the NanoString miRNA Expression Assay. The expression level of candidate miRNAs were then validated by quantitative reverse transcription-PCR (qRT-PCR) method. Findings: The discovery cohort (N=19) lead to the identification of 37 differentially expressed miRNAs between the two groups. Six miRNAs (miR122-5p, miR1246, miR1303, miR574-5p, miR30d-5p, and miR424-5p) were selected and further validated in the larger cohort (N=135). The qRT-PCR analysis confirmed that the six miRNAs expression levels were significantly higher in the severe dengue group compared to the non-severe group. Based on receiver operating characteristic (ROC) analysis, miR574-5p and miR1246 displayed the highest diagnostic performance in discriminating between severe from non-severe dengue (AROC curve =0·83). Additionally, miR574-5p and miR1246 had high sensitivity and high negative predictive value for detecting severe dengue. Multivariate analysis suggested that serum miR574-5p was an independent predictor of severe dengue (odds ratio 3·30, 95% CI 1·81-6·04; p<0·001). Interpretation: Circulating miRNAs, especially miR-574-5p and miR-1246, could be promising diagnostic and prognostic biomarkers for severe dengue.
2022-10-26 | GSE190749 | GEO
Project description:BackgroundLeptospirosis, a global zoonotic infectious disease, has various clinical manifestations ranging from mild self-limiting illness to life-threatening with multi-organ damage, including liver involvement. This study was aimed at identifying circulating microRNAs (miRNAs) as novel biomarkers for predicting severe liver involvement in patients with leptospirosis.MethodsIn a discovery set, 12 serum samples of patients with anicteric and icteric leptospirosis at initial clinical presentation were used for miRNA profiling by a NanoString nCounter miRNA assay. In a validated cohort, top candidate miRNAs were selected and further tested by qRT-PCR in serum samples of 81 and 16 individuals with anicteric and icteric leptospirosis, respectively.ResultsThe discovery set identified 38 significantly differential expression miRNAs between the two groups. Among these, miR-601 and miR-630 were selected as the top two candidates significantly up-regulated expressed in the icteric group. The enriched KEGG pathway showed that these miRNAs were mainly involved in immune responses and inflammation. In the validated cohort, miR-601 and miR-630 levels were significantly higher in the icteric group compared with the anicteric group. Additionally, these two miRNAs displayed good predictors of subsequent acute liver failure with a high sensitivity of 100%. On regression analysis, elevated miR-601 and miR-630 expression were also predictive of multi-organ failures and poor overall survival.ConclusionOur data indicated that miRNA expression profiles were significantly differentiated between the icteric and anicteric groups. Serum miR-601 and miR-630 at presentation could potentially serve as promising biomarkers for predicting subsequent acute liver failure and overall survival in patients with leptospirosis.
| S-EPMC8476044 | biostudies-literature
Project description:Background: Preeclampsia (PE) is a placental disease characterized by hypertension and proteinuria in pregnant women, which is associated with a high maternal and infantile morbidity. However, circulating biomarkers able to predict the prognosis of PE are lacking. Methods: Thirty-eight women were included in the study. They consisted of 19 patients with PE (13 with severe PE and 6 women with non-severe PE) and 19 gestational age-matched normal pregnancy controls. We measured coagulation pathway, endothelial responses and microparticle release and circulating gene expression in PE patient groups and normotensive controls. Results: The measurement of markers associated with coagulation pathway, endothelial activation and circulating microparticles enabled to discriminate PE from normal pregnancy but were not sufficient to distinguish severe from non-severe PE. PE patients also exhibited a specific transcriptional program distinct from that of control women and subtle differences were observed between severe and non-severe PE. Functional annotation of the up-modulated signature in PE highlighted two main functions related to ribosome and complement. Importantly, we found that 8 genes were specifically up-modulated in severe preeclampsia. Among these genes, the expression of VSIG4 was significantly increased in patients with severe preeclampsia in comparison with controls and patients with non-severe preeclampsia. Conclusion: Using transcriptional signatures of blood samples, we identified the gene encoding the estrogen receptor as a potential diagnostic marker of severe preeclampsia. In addition, the determination of this gene may improve the prognostic assessment of severe preeclampsia. Thirty-eight women were included in the study: 19 patients with PE, including 6 women with non-severe PE and 13 with severe PE, and 19 women with normal pregnancy (NP) selected according to age, weight, smoking status, race, gestational age at the inclusion, and blood pH (Table 1 of manuscript). Women with NP had no history of medical illness or medication, and received routing prenatal care. The diagnostic of PE was based on a blood pressure of M-bM-^IM-% 140/90 mmHg taken twice, uricemia above normal laboratory range (120-420 M-BM-5mol/L), and proteinuria higher than 300 mg in a 24 hour-collection, occurring after 20 gestational weeks in previously normotensive women (Table 2). The criteria used to define severe PE included one of the following conditions: a blood pressure higher than 160/110 mmHg, a proteinuria higher than 1500 mg/24h), a multisystem disorder, maternal cerebral symptoms (seizures, stroke) or intrauterine growth restriction below the 3M-BM-0 percentile. Women with multiple gestations, fetal congenital malformations/chromosomal abnormalities, recent infection, antiphospholipid antibodies, trauma, drug or alcohol abuse during pregnancy, preexisting hypertension, thrombophilia with PE history, or women receiving anticoagulant or antiaggregation therapy were excluded from the study. Two microarrays (one non-severe PE and one normal) were discarded from the analysis for technical reasons. Thus, only 36 microarrays are included here.
2014-05-14 | E-GEOD-48424 | biostudies-arrayexpress
Project description:Background: Preeclampsia (PE) is a placental disease characterized by hypertension and proteinuria in pregnant women, which is associated with a high maternal and infantile morbidity. However, circulating biomarkers able to predict the prognosis of PE are lacking. Methods: Thirty-eight women were included in the study. They consisted of 19 patients with PE (13 with severe PE and 6 women with non-severe PE) and 19 gestational age-matched normal pregnancy controls. We measured coagulation pathway, endothelial responses and microparticle release and circulating gene expression in PE patient groups and normotensive controls. Results: The measurement of markers associated with coagulation pathway, endothelial activation and circulating microparticles enabled to discriminate PE from normal pregnancy but were not sufficient to distinguish severe from non-severe PE. PE patients also exhibited a specific transcriptional program distinct from that of control women and subtle differences were observed between severe and non-severe PE. Functional annotation of the up-modulated signature in PE highlighted two main functions related to ribosome and complement. Importantly, we found that 8 genes were specifically up-modulated in severe preeclampsia. Among these genes, the expression of VSIG4 was significantly increased in patients with severe preeclampsia in comparison with controls and patients with non-severe preeclampsia. Conclusion: Using transcriptional signatures of blood samples, we identified the gene encoding the estrogen receptor as a potential diagnostic marker of severe preeclampsia. In addition, the determination of this gene may improve the prognostic assessment of severe preeclampsia.
2014-05-14 | GSE48424 | GEO
Project description:Discovery and validation of circulating miRNAs for the clinical prognosis of severe dengue
| PRJNA788392 | ENA
Project description:Gene expression profiling of whole blood in patients with severe leptospirosis
| PRJNA823595 | ENA