Dataset Information

Integrated Multi-Omics Analysis of Dampness-Heat Gout Reveals Diagnostic Biomarkers and Therapeutic Targets

ABSTRACT:

Damp-heat gout (DHG) is a clinically recognized subtype of gout characterized by a specific syndrome in traditional Chinese medicine (TCM). However, its pathomechanism remains unclear, and there is a lack of quantifiable indicators for accurate clinical diagnosis and treatment. This study aimed to elucidate the pathological mechanisms underlying DHG and to establish a symptom-centered model for its diagnosis and treatment. A total of 136 participants, comprising healthy controls and diagnosed DHG patients, were recruited for the analysis. Utilizing serum metabolomics and proteomics methodologies, we identified 21 common pathways associated with DHG, highlighting four crucial pathways: bile secretion, cholesterol metabolism, purine metabolism, and arachidonic acid metabolism, which were found to correlate significantly with the primary symptoms of DHG. Additionally, six key biomarkers—hypoxanthine, prostaglandin E2, uric acid, deoxycholic acid, taurochenodeoxycholic acid, and bilirubin—were identified. These biomarkers demonstrated robust diagnostic potential, with AUC values of 0.987 in the discovery cohort and above 0.99 in the validation cohort.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive - reverse phase

PROVIDER: MTBLS12820 | MetaboLights | 2026-02-04

REPOSITORIES: MetaboLights

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	a_MTBLS12820_LC-MS_negative_reverse-phase_metabolite_profiling.txt	Txt
	a_MTBLS12820_LC-MS_positive_reverse-phase_metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS12820_LC-MS_negative_reverse-phase_metabolite_profiling_v2_maf.tsv	Tabular
	m_MTBLS12820_LC-MS_positive_reverse-phase_metabolite_profiling_v2_maf.tsv	Tabular

Items per page:

1 - 5 of 6

Similar Datasets

Project description:The major aetiological risk factor for Barrett's oesophagus and oesophageal adenocarcinoma is gastroesophageal reflux. This study's aim was to identify genes involved in the celular response to reflux in vitro. The Barrettâ??s oesophagus cell line, CP-A hTERT, was exposed to media with acid, deoxycholic acid or a primary bile salt mixture. RNA expression was compared with controls on Affymetrix U133 Plus 2.0 arrays. In CP-A hTERT, the greatest number of changes in gene expression was observed after treatment with deoxycholic acid, pH 4.5; 152 genes were up-regulated at 2 hours (91 at 6 hours) and 10 down-regulated at 2 hours (34 at 6 hours). 12 genes were identified and were subsequently assessed in patients with non-erosive reflux disease, oesophagitis, Barrett's oesophagus and oesophageal adenocarcinoma; Background and Aims: The major etiological risk factor for Barrettâ??s esophagus and esophageal adenocarcinoma is gastro-esophageal reflux. This studyâ??s aim was to identify genes involved in the cellular response to components of reflux both in vitro and in patients with reflux-related disease. Methods: The Barrettâ??s cell line, CP-A hTERT, was exposed to media with acid, deoxycholic acid or a primary bile salt mixture. RNA expression was compared with controls on Affymetrix U133 Plus 2.0 arrays. 12 genes of interest were analysed by Real Time PCR both in cell line and biopsies from 110 patients with non-erosive reflux disease, esophagitis, Barrettâ??s esophagus and esophageal adenocarcinoma. Results: In CP-A hTERT, the greatest number of changes in gene expression was observed after treatment with deoxycholic acid, pH 4.5. Of 12 genes analysed in biopsies, 10 were significantly different between the 4 groups with the largest change for anterior gradient homolog 2, which may modulate p53 function. This had highest expression in biopsies from Barrettâ??s esophagus (median gene fold change for Barrettâ??s esophagus versus non-erosive reflux disease, 411.2 (95% CI 290.5-682.7; p<0.01); esophageal adenocarcinoma versus non-erosive reflux disease 68.1 (20.5-161.4; p<0.01)). In addition 4 genes associated with development/differentiation were upregulated in Barrettâ??s biopsies compared to those from non-erosive reflux disease (SEL1L, MFNG, CRIP1 and EFNA1). Conclusions: Novel genes have been identified, whose expression is altered after acid and bile exposure in vitro and in biopsies from patients with reflux related diseases. These genes may have utility as biomarkers of response to reflux and should be assessed in prospective studies. Experiment Overall Design: The Barrett's oesophagus cell line CP-A hTERT was treated with a 15 minute exposure of acid (pH 4.5), a mixture of primary bile acids (pH 4.5) or deoxycholic acid (pH 4.5). RNA extraction occurred in treatment and non-treated cells at 2 hours and 6 hours. The treatments were performed in duplicate on 2 different days. RNA was compared in each treatment to each control at the relevant time points, in a 2 x 2 manner by using Affymetrex U133 Plus 2.0 arrays. Results of 12 genes were confirmed by Real Time PCR and were subsequently assessed in patients with non-erosive reflux disease, oesophagitis, Barrett's oesophagus and oesophageal adenocarcinoma.

Project description:The major aetiological risk factor for Barrett's oesophagus and oesophageal adenocarcinoma is gastroesophageal reflux. This study's aim was to identify genes involved in the celular response to reflux in vitro. The Barrett’s oesophagus cell line, CP-A hTERT, was exposed to media with acid, deoxycholic acid or a primary bile salt mixture. RNA expression was compared with controls on Affymetrix U133 Plus 2.0 arrays. In CP-A hTERT, the greatest number of changes in gene expression was observed after treatment with deoxycholic acid, pH 4.5; 152 genes were up-regulated at 2 hours (91 at 6 hours) and 10 down-regulated at 2 hours (34 at 6 hours). 12 genes were identified and were subsequently assessed in patients with non-erosive reflux disease, oesophagitis, Barrett's oesophagus and oesophageal adenocarcinoma Background and Aims: The major etiological risk factor for Barrett’s esophagus and esophageal adenocarcinoma is gastro-esophageal reflux. This study’s aim was to identify genes involved in the cellular response to components of reflux both in vitro and in patients with reflux-related disease. Methods: The Barrett’s cell line, CP-A hTERT, was exposed to media with acid, deoxycholic acid or a primary bile salt mixture. RNA expression was compared with controls on Affymetrix U133 Plus 2.0 arrays. 12 genes of interest were analysed by Real Time PCR both in cell line and biopsies from 110 patients with non-erosive reflux disease, esophagitis, Barrett’s esophagus and esophageal adenocarcinoma. Results: In CP-A hTERT, the greatest number of changes in gene expression was observed after treatment with deoxycholic acid, pH 4.5. Of 12 genes analysed in biopsies, 10 were significantly different between the 4 groups with the largest change for anterior gradient homolog 2, which may modulate p53 function. This had highest expression in biopsies from Barrett’s esophagus (median gene fold change for Barrett’s esophagus versus non-erosive reflux disease, 411.2 (95% CI 290.5-682.7; p<0.01); esophageal adenocarcinoma versus non-erosive reflux disease 68.1 (20.5-161.4; p<0.01)). In addition 4 genes associated with development/differentiation were upregulated in Barrett’s biopsies compared to those from non-erosive reflux disease (SEL1L, MFNG, CRIP1 and EFNA1). Conclusions: Novel genes have been identified, whose expression is altered after acid and bile exposure in vitro and in biopsies from patients with reflux related diseases. These genes may have utility as biomarkers of response to reflux and should be assessed in prospective studies. Keywords: Acid (pH 4.5) and bile (mixture of primary bile salts or the secondary bile salt deoxycholic acid, both at pH 4.5) challenge to a Barrett's oesophagus cell line. RNA extraction at 2 and 6 hours. Comparison of treatment RNA to control (non-treatment) RNA,

Dataset Information

Integrated Multi-Omics Analysis of Dampness-Heat Gout Reveals Diagnostic Biomarkers and Therapeutic Targets

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets