Development of a novel non-invasive biomarker panel for hepatic fibrosis in individuals with MASLD
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ABSTRACT:
PROVIDER: PRJNA1005170 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25630200_1.fastq.gz | Fastqsanger.gz | |||
| SRR25630200_2.fastq.gz | Fastqsanger.gz | |||
| SRR25630201_1.fastq.gz | Fastqsanger.gz | |||
| SRR25630201_2.fastq.gz | Fastqsanger.gz | |||
| SRR25630202_1.fastq.gz | Fastqsanger.gz |
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Project description:- Background & Aims: Considering the escalating prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and MASLD-related fibrosis, accurate non-invasive biomarkers for diagnosis and staging of fibrosis are urgently needed. This study Aims to develop a blood-based biomarker panel for fibrosis detection in individuals with MASLD. - Approach & Results: Using a translational diet-induced LDLr-/-.Leiden MASLD mouse model, candidate biomarkers were identified focused on the mechanism of collagen deposition, by integrating hepatic gene expression and new extracellular matrix deposition, as detected by dynamic D2O-labeling. To translate these findings to humans, gene expression profiles and biomarkers were analyzed in liver biopsies and serum samples from 67 individuals with histologically characterized MASLD and variable degrees of fibrosis. This led to the selection of three biomarkers for a blood-based fibrosis biomarker panel: IGFBP7, SSc5D and Sema4D. The accuracy of the biomarker panel was tested in a separate cohort of 128 individuals with histologically characterized MASLD across different stages of fibrosis. A Light Gradient Boosting Machine (LGBM) model was applied to predict fibrosis stage in MASLD (F0/F1: AUC = 0.90; F2: AUC = 0.91; F3/F4: AUC = 0.87). - Conclusion & Discussion: Using a translational Approach to identify collagen turnover related proteins indicative of fibrosis, we developed an accurate blood-based biomarker panel to detect and stage hepatic fibrosis in individuals with MASLD.
2024-05-17 | GSE240729 | GEO
Project description:Purpose: Gastric cancer (GC) is one of the most common causes of cancer deaths worldwide; however, reliable and non-invasive screening methods for GC are not established. Therefore, we conducted this study to develop a biomarker for GC detection, consisting of urinary microRNAs (miRNAs). Experimental Design: We matched 306 participants by age and sex (153 pairs consisting of patients with GC and healthy controls [HCs]), then randomly divided them across three groups: (1) the discovery cohort (4 pairs); (2) the training cohort (95 pairs); (3) the validation cohort (54 pairs). Moreover, 64 participants (32 pairs) with serum samples were also enrolled in the serum cohort. Result: There were 22 urinary miRNAs with significantly aberrant expressions between the two groups in the discovery cohort. Upon multivariate analysis of the training cohort, urinary expression levels of miR-6807-5p and miR-6856-5p were significantly independent biomarkers for diagnosis of GC, in addition to Helicobacter pylori (H. pylori) status. A diagnostic panel that combined the aberrant miRNAs and H. pylori status distinguished between HC and GC samples with an area under the curve (AUC) = 0.736. In the validation cohort, urinary miR-6807-5p and miR-6856-5p showed significantly higher expression levels in the GC group, and the combination biomarker panel of miR-6807-5p, miR-6856-5p, and H. pylori status also showed excellent performance (AUC = 0.885). In addition, serum levels of miR-6807-5p and miR-6856-5p were significantly higher in the GC group. Conclusion: This novel biomarker panel enables early and non-invasive detection of GC.
2019-12-22 | GSE128720 | GEO
Project description:use serum lipids panel to distinguish human fibrosis and non-fibrosis liver
2024-06-27 | PXD051283 |
Project description:Early-onset preeclampsia (EOPE) is a severe pregnancy complication associated with significant maternal and fetal morbidity and mortality. Currently, there is a critical need for accurate, non-invasive biomarkers to facilitate early diagnosis and effective management of EOPE. In this study, we aimed to investigate the transcriptional alterations and non-invasive biomarker potential of peripheral blood microRNAs in patients with EOPE. Through our research, we successfully identified two reliable plasma miRNA biomarkers and proposed a circulating two-miRNA panel for the non-invasive early detection of EOPE. Additionally, we independently validated our findings in different patient cohorts using various technological platforms.
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Project description:Metabolic dysfunction-associated steatotic liver disease (MASLD), closely associated with obesity, can progress to metabolic dysfunction-associated steatohepatitis when the liver undergoes overt inflammatory damage. A-kinase anchoring protein 1 (AKAP1) has been shown to control lipid accumulation in brown adipocytes. However, the role of AKAP1 signaling in hepatic lipid metabolism and MASLD remains poorly understood. Here, we showed that hepatocyte-specific AKAP1 deficiency exacerbated hepatic steatosis and steatohepatitis in male mice subjected to a high-fat diet and fast-food diet, respectively. Mechanistically, AKAP1 directly phosphorylated and inactivated glycerol-3-phosphate acyltransferase 1 (GPAT1) in a PKA-dependent manner, thus suppressing lysophosphatidic acid (LPA) production. Increased endogenous LPA in hepatocytes promoted hepatocellular triglyceride (TG) synthesis and initiated pronounced inflammatory response in Kupffer cells. Restoring hepatic AKAP1 or repressing LPA levels via GPAT1 knockdown alleviated MASLD exacerbation. Overall, AKAP1 plays a protective role against MASLD by inhibiting GPAT1 activity, highlighting the potential of targeting AKAP1/PKA/GPAT1 signalosome for MASLD therapy.
2025-05-26 | PXD062388 | Pride
Project description:Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are characterized by excessive triglyceride accumulation in the liver. However, due to an incomplete understanding of its pathogenesis, more efforts are still needed to identify specific and effective treatments. N4-acetylcytidine (ac4C) is a newly discovered RNA modification to regulate mRNA stability post-transcriptionally. N-acetyltransferase 10 (NAT10), the sole enzyme catalyzing mRNA acetylation, has not been fully explored in human diseases, especially in MASLD and MASH. In the current study, abundant RNA acetylation was found in lipid metabolism-related genes in the livers of leptin receptor-deficient (db/db) mice. Besides, hepatic NAT10 expression is significantly increased in multiple mouse models of MASLD and MASH. NAT10 expression is also elevated in patients with MASLD and positively correlated with clinical characteristics. Genetic NAT10 knockdown protects against diet-induced hepatic steatosis and steatohepatitis in mice, while its overexpression exacerbates steatosis. Mechanistically, NAT10 could bind to Srebp-1c mRNA to promote its stability and expression, thereby upregulating lipogenic enzymes. In addition, the translational significance of our findings is that treatment of Remodelin, an NAT10 inhibitor, could improve liver steatosis and dyslipidemia in a preclinical mouse model. Together, these findings highlight the significance of ac4C modification and NAT10 in MASLD and MASH, offering a potential therapeutic target for disease treatment.
2024-09-22 | GSE275575 | GEO
Project description:Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are characterized by excessive triglyceride accumulation in the liver. However, due to an incomplete understanding of its pathogenesis, more efforts are still needed to identify specific and effective treatments. N4-acetylcytidine (ac4C) is a newly discovered RNA modification to regulate mRNA stability post-transcriptionally. N-acetyltransferase 10 (NAT10), the sole enzyme catalyzing mRNA acetylation, has not been fully explored in human diseases, especially in MASLD and MASH. In the current study, abundant RNA acetylation was found in lipid metabolism-related genes in the livers of leptin receptor-deficient (db/db) mice. Besides, hepatic NAT10 expression is significantly increased in multiple mouse models of MASLD and MASH. NAT10 expression is also elevated in patients with MASLD and positively correlated with clinical characteristics. Genetic NAT10 knockdown protects against diet-induced hepatic steatosis and steatohepatitis in mice, while its overexpression exacerbates steatosis. Mechanistically, NAT10 could bind to Srebp-1c mRNA to promote its stability and expression, thereby upregulating lipogenic enzymes. In addition, the translational significance of our findings is that treatment of Remodelin, an NAT10 inhibitor, could improve liver steatosis and dyslipidemia in a preclinical mouse model. Together, these findings highlight the significance of ac4C modification and NAT10 in MASLD and MASH, offering a potential therapeutic target for disease treatment.
2024-09-22 | GSE275576 | GEO
Project description:A novel urinary microRNA biomarker panel for detecting gastric cancer
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Project description:Uric acid has garnered increasing attention for its association with metabolic dysfunction-associated steatotic liver disease (MASLD) in recent cross-sectional studies, although detailed understanding of its involvement remains limited. This study confirms a strong association between urate levels and elevated risk of both MASLD and type 2 diabetes (T2D) through a large-scale observational analysis of UK Biobank data. However, Mendelian randomization (MR) analysis involving over 2 million samples identified only causal effects of urate on serum triglyceride levels and the risk of T2D. Additionally, a targeted metabolomics study involving elderly Chinese participants revealed that, rather than UA, allantoin—a byproduct of UA oxidation—was significantly elevated in individuals with dyslipidemia or T2D. Notably, a significant negative correlation was found between serum allantoin level and fasting glucose, as well as serum triglyceride and cholesterol levels. Animal studies demonstrated that allantoin exacerbates hepatic lipid accumulation and glucose intolerance in mice fed a high-fat diet, which was accompanied by increased hepatic lipid biogenesis and reduced bile acid production. Interestingly, our findings indicate that allantoin exhibits a strong binding affinity for PPARα, suggesting that it may act as an inhibitor of PPARα, thereby promoting the progression of MASLD. These results underscore the critical role of allantoin, rather than UA, in the development of MASLD, offering valuable insights for the prediction and management of hepatic metabolic disorders.
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Project description:Allantoin promotes MASLD progression
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