Dataset Information

Clinical Application Value of Ceramide and Sphingomyelin as Biomarkers for the Diagnosis of Drug-Induced Liver Injury

ABSTRACT:

Background : Drug-induced liver injury (DILI) is a serious health concern that presents challenges in early detection and accurate diagnosis, thereby complicating the treatment of this liver disease. Therefore, it is crucial to explore specific biomarkers to improve the accuracy of diagnosing DILI.

Methods : A study was conducted involving patients with DILI, non-drug-related benign liver diseases (NDILI), and healthy controls (HCs). Serum metabolomic profiles were analyzed using liquid chromatography-mass spectrometry (LC-MS), and transcriptomic data were retrieved from public datasets for integrated analysis. Biomarkers and cytokines were detected using enzyme-linked immunosorbent assays (ELISA). Differential metabolites were identified through multi-omics joint analysis, large sample validation, and logistic regression models.

Results: Transcriptomic analyses highlighted that inflammatory and metabolic pathways are critical to DILI pathogenesis. Integrated transcriptomic-metabolomic analysis revealed significant alterations in sphingolipid metabolism, with ceramide and sphingomyelin emerging as key metabolites for distinguishing DILI, NDILI, and HCs. The multivariable diagnostic model combining ceramide, sphingomyelin, and traditional biomarkers demonstrated superior performance. Notably, levels of IL-6 and IL-8 were significantly elevated in DILI patients compared to HCs.

Conclusion: This study preliminarily determined that ceramides and sphingolipids are significantly elevated in DILI compared to NDILI and HCs. Their combination with traditional liver function indicators further improves the diagnostic accuracy of DILI. Therefore, ceramides and sphingolipids may serve as potential biomarkers for the diagnosis and management of DILI.

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

PROVIDER: MTBLS12765 | MetaboLights | 2025-07-23

REPOSITORIES: MetaboLights

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			Action	DRS
	a_MTBLS12765_LC-MS_negative_hilic_metabolite_profiling.txt	Txt
	a_MTBLS12765_LC-MS_positive_hilic_metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS12765_LC-MS_negative_hilic_metabolite_profiling_v2_maf.tsv	Tabular
	m_MTBLS12765_LC-MS_positive_hilic_metabolite_profiling_v2_maf.tsv	Tabular

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Project description:We have used human umbilical vein endothelial cell line (HUVEC) as a model to investigate the effect of ultrasound (US) activated micro-bubbles on sensitizing the tumour response to radiation and to check the implication of this approach on gene expression. The use of micro-bubbles in cancer therapy is a novel approach that is being recently investigated, and patterns of gene expressions were not yet characterized. Gene analysis has identified about 19,264 genes; where, 239 – 517 genes have shown more than two folds up-regulation in response to the different treatments. This included a number of genes that are known to be involved in apoptosis and ceramide-induced apoptosis pathways, such as Sphingomyelin phosphodiesterase 2, neutral sphingomyelinase (SMPD2), sphingomyelin phosphodiesterase 1, acid lysosomal (ASM; SMPD1), UDP-galactose ceramide galactosyltransferase (UGT8), cytochrome c oxidase (COX6B1), Caspase-9 and mitogen-activated protein kinase kinase 1 (MAP2K1). To verify these results, we have performed Real time RT-PCR, which indicated an up-regulation that ranged from 2 to 200 folds, specifically in the combined treatment of US, 3.3% micro-bubbles and 8 Gy. The observed higher levels of expression of UGT8, SMPD2 and Caspase 9-alpha when compared to the control or to radiation only indicated the involvement of ceramide, which possibly induces apoptosis . These results support the hypothesis that micro-bubbles play a role in increasing sensitization to radiation, and can prove to be an effective cancer therapeutic approach. Gene analysis has identified about 19,264 genes; where, 239 – 517 genes have shown more than two folds up-regulation in response to the different treatments. This included a number of genes that are known to be involved in apoptosis and ceramide-induced apoptosis pathways, such as Sphingomyelin phosphodiesterase 2, neutral sphingomyelinase (SMPD2), sphingomyelin phosphodiesterase 1, acid lysosomal (ASM; SMPD1), UDP-galactose ceramide galactosyltransferase (UGT8), cytochrome c oxidase (COX6B1), Caspase-9 and mitogen-activated protein kinase kinase 1 (MAP2K1). To verify these results, we have performed Real time RT-PCR, which indicated an up-regulation that ranged from 2 to 200 folds, specifically in the combined treatment of US, 3.3% micro-bubbles and 8 Gy. The observed higher levels of expression of UGT8, SMPD2 and Caspase 9-alpha when compared to the control or to radiation only indicated the involvement of ceramide, which possibly induces apoptosis . These results support the hypothesis that micro-bubbles play a role in increasing sensitization to radiation, and can prove to be an effective cancer therapeutic approach.

Dataset Information

Clinical Application Value of Ceramide and Sphingomyelin as Biomarkers for the Diagnosis of Drug-Induced Liver Injury

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