Prognostic Liver Signature profiles in biopsy tissues from non-alcoholic fatty liver disease (NAFLD) patients in the U.S.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA633480 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Background/Aims: There is a major unmet need to assess prognostic impact of anti-fibrotics in clinical trials due to the slow rate of liver fibrosis progression. We aimed to develop a surrogate biomarker to predict future fibrosis progression. Methods: A Fibrosis Progression Signature (FPS) was defined to predict fibrosis progression within 5 years in HCV and NAFLD patients with no to minimal fibrosis at baseline (n=421), and validated in an independent NAFLD cohort (n=78). The FPS was used to assess response to 13 candidate anti-fibrotics in organotypic ex vivo cultures of clinical fibrotic liver tissues (n=78), and cenicriviroc in NASH patients enrolled in a clinical trial (n=19, NCT02217475). A serum-protein-based surrogate FPS (FPSec) was developed and technically evaluated in a liver disease patient cohort (n=79). Results: A 20-gene FPS was defined and validated in an independent NAFLD cohort (aOR=10.93, AUROC=0.86). Among computationally inferred fibrosis-driving FPS genes, BCL2 was confirmed as a potential pharmacological target using clinical liver tissues. Systematic ex vivo evaluation of 13 candidate anti-fibrotics identified rational combination therapies based on epigallocatechin gallate, some of which were validated for enhanced anti-fibrotic effect in ex vivo culture of clinical liver tissues. In NASH patients treated with cenicriviroc, FPS modulation was associated with 1-year fibrosis improvement accompanied by suppression of the E2F pathway. Induction of PPARalpha pathway was absent in patients without fibrosis improvement, suggesting benefit of combining PPARalpha agonism to improve anti-fibrotic efficacy of cenicriviroc. A 7-protein FPSec panel showed concordant prognostic prediction with FPS. Conclusion: FPS predicts long-term fibrosis progression in an etiology-agnostic manner, which can inform anti-fibrotic drug development.
2021-12-22 | GSE150734 | GEO
Project description:Non-alcoholic fatty liver disease (NAFLD) is a major global health problem with its high prevalence and risk of developing lethal complications, progressive liver fibrosis and hepatocellular carcinoma (HCC), the only rising cancer mortality in the U.S. For early HCC detection to improve the dismal prognosis, there is an urgent unmet need to identify a subset of NAFLD patients with elevated risk of HCC. Herein, we derived a hepatic-transcriptome-based NAFLD-specific HCC risk biomarker, PLS-NAFLD, and validated it in two independent cohorts of HCC-naive and experienced NAFLD patients..
2022-07-01 | GSE192959 | GEO
Project description:Background/Aims: There is a major unmet need to assess prognostic impact of anti-fibrotics in clinical trials due to the slow rate of liver fibrosis progression. We aimed to develop a surrogate biomarker to predict future fibrosis progression. Methods: A Fibrosis Progression Signature (FPS) was defined to predict fibrosis progression within 5 years in HCV and NAFLD patients with no to minimal fibrosis at baseline (n=421), and validated in an independent NAFLD cohort (n=78). The FPS was used to assess response to 13 candidate anti-fibrotics in organotypic ex vivo cultures of clinical fibrotic liver tissues (n=78), and cenicriviroc in NASH patients enrolled in a clinical trial (n=19, NCT02217475). A serum-protein-based surrogate FPS (FPSec) was developed and technically evaluated in a liver disease patient cohort (n=79). Results: A 20-gene FPS was defined and validated in an independent NAFLD cohort (aOR=10.93, AUROC=0.86). Among computationally inferred fibrosis-driving FPS genes, BCL2 was confirmed as a potential pharmacological target using clinical liver tissues. Systematic ex vivo evaluation of 13 candidate anti-fibrotics identified rational combination therapies based on epigallocatechin gallate, some of which were validated for enhanced anti-fibrotic effect in ex vivo culture of clinical liver tissues. In NASH patients treated with cenicriviroc, FPS modulation was associated with 1-year fibrosis improvement accompanied by suppression of the E2F pathway. Induction of PPARalpha pathway was absent in patients without fibrosis improvement, suggesting benefit of combining PPARalpha agonism to improve anti-fibrotic efficacy of cenicriviroc. A 7-protein FPSec panel showed concordant prognostic prediction with FPS. Conclusion: FPS predicts long-term fibrosis progression in an etiology-agnostic manner, which can inform anti-fibrotic drug development.
2021-12-22 | GSE161841 | GEO
Project description:Non-alcoholic fatty liver disease (NAFLD) is a major global health problem with its high prevalence and risk of developing lethal complications, progressive liver fibrosis and hepatocellular carcinoma (HCC), the only rising cancer mortality in the U.S. For early HCC detection to improve the dismal prognosis, there is an urgent unmet need to identify a subset of NAFLD patients with elevated risk of HCC. Herein, we derived a hepatic-transcriptome-based NAFLD-specific HCC risk biomarker, PLS-NAFLD, and validated it in two independent cohorts of HCC-naive and experienced NAFLD patients..
2022-07-01 | GSE193080 | GEO
Project description:Non-alcoholic fatty liver disease (NAFLD) is a major global health problem with its high prevalence and risk of developing lethal complications, progressive liver fibrosis and hepatocellular carcinoma (HCC), the only rising cancer mortality in the U.S. For early HCC detection to improve the dismal prognosis, there is an urgent unmet need to identify a subset of NAFLD patients with elevated risk of HCC. Herein, we derived a hepatic-transcriptome-based NAFLD-specific HCC risk biomarker, PLS-NAFLD, and validated it in two independent cohorts of HCC-naive and experienced NAFLD patients.
2022-07-01 | GSE193066 | GEO
Project description:Prognostic Liver Signature profiles in biopsy tissues from non-alcoholic fatty liver disease (NAFLD) patients in Japan
| PRJNA679603 | ENA
Project description:We investigated the hepatic transcriptome of 58 biopsy-proven NAFLD patients at multiple stages of the disease (NAFL, NASH with mild fibrosis, NASH with advanced fibrosis) with the aim of describing the pathophysiological events driving the development and progression of NASH.
2021-04-14 | E-MTAB-9815 | biostudies-arrayexpress
Project description:Background & Aims: Cirrhosis and liver cancer are potential outcomes of advanced nonalcoholic fatty liver disease (NAFLD). It is not clear what factors determine whether patients will develop advanced or mild NAFLD, limiting non-invasive diagnosis and treatment before clinical sequelae emerge. We investigated whether DNA methylation profiles can distinguish patients with mild disease from those with advanced NAFLD, and how these patterns are functionally related to hepatic gene expression. Methods: We collected frozen liver biopsies and clinical data from patients with biopsy-proven NAFLD (56 in the discovery cohort and 34 in the replication cohort). Samples were divided into groups based on histologic severity of fibrosis: F0?1 (mild) and F3?4 (advanced). DNA methylation profiles were determined and coupled with gene expression data from the same biopsies; differential methylation was validated in subsets of the discovery and replication cohorts. We then analyzed interactions between the methylome and transcriptome. Results: Clinical features did not differ between patients known to have mild or advanced fibrosis based on biopsy analysis. There were 69,247 differentially methylated CpG sites (76% hypomethylated, 24% hypermethylated) in patients with advanced vs mild NAFLD (P<.05). Methylation at FGFR2, MAT1A, and CASP1 was validated by bisulfite pyrosequencing and the findings were reproduced in the replication cohort. Methylation correlated with gene transcript levels for 7% of differentially methylated CpG sites, indicating that differential methylation contributes to differences in expression. In samples with advanced NAFLD, many tissue repair genes were hypomethylated and overexpressed, whereas genes in certain metabolic pathways, including 1-carbon metabolism, were hypermethylated and under-expressed. Conclusions: Functionally relevant differences in methylation can distinguish patients with advanced vs mild NAFLD. Altered methylation of genes that regulate processes such as steatohepatitis, fibrosis, and carcinogenesis indicate the role of DNA methylation in progression of NAFLD. Three technical replicates were included for quality control along with 35 mild NAFLD (33 unique samples) and 24 advanced NAFLD (23 unique sample). One sample per technical duplication was randomly included for a total of 56 NAFLD samples used for study.
2013-08-30 | E-GEOD-49542 | biostudies-arrayexpress
Project description:FLORINASH - The role of intestinal microflora in non-alcoholic fatty liver disease (NAFLD) EU FP7-HEALTH, project number 241913<br>Florinash examined the role on the gut microbiota in NAFLD. Metagenomic, proteomic, metabolomic and transcriptomic data were integrated to give provide a systems biology approach to disease-associated studies. Liver biopsies were obtained from patients undergoing bariatric surgery; one was used to diagnose NAFLD, the other was used to examine the host transcriptome in NAFLD. This dataset is part of the TransQST collection.
2018-03-15 | E-MTAB-4856 | biostudies-arrayexpress
Project description:Background/Aims: There is a major unmet need to assess prognostic impact of anti-fibrotics in clinical trials due to the slow rate of liver fibrosis progression. We aimed to develop a surrogate biomarker to predict future fibrosis progression. Methods: A Fibrosis Progression Signature (FPS) was defined to predict fibrosis progression within 5 years in HCV and NAFLD patients with no to minimal fibrosis at baseline (n=421), and validated in an independent NAFLD cohort (n=78). The FPS was used to assess response to 13 candidate anti-fibrotics in organotypic ex vivo cultures of clinical fibrotic liver tissues (n=78), and cenicriviroc in NASH patients enrolled in a clinical trial (n=19, NCT02217475). A serum-protein-based surrogate FPS (FPSec) was developed and technically evaluated in a liver disease patient cohort (n=79). Results: A 20-gene FPS was defined and validated in an independent NAFLD cohort (aOR=10.93, AUROC=0.86). Among computationally inferred fibrosis-driving FPS genes, BCL2 was confirmed as a potential pharmacological target using clinical liver tissues. Systematic ex vivo evaluation of 13 candidate anti-fibrotics identified rational combination therapies based on epigallocatechin gallate, some of which were validated for enhanced anti-fibrotic effect in ex vivo culture of clinical liver tissues. In NASH patients treated with cenicriviroc, FPS modulation was associated with 1-year fibrosis improvement accompanied by suppression of the E2F pathway. Induction of PPAR-alfa pathway was absent in patients without fibrosis improvement, suggesting benefit of combining PPAR-alfa agonism to improve anti-fibrotic efficacy of cenicriviroc. A 7-protein FPSec panel showed concordant prognostic prediction with FPS. Conclusion: FPS predicts long-term fibrosis progression in an etiology-agnostic manner, which can inform anti-fibrotic drug development.
2021-12-22 | GSE182060 | GEO