Identification and characterization of lysophosphatidylcholine 14:0 as a biomarker for drug-induced lung disease

Saito, Kosuke; Gemma, Akihiko; Hattori, Noboru; Ushiki, Atsuhito; Tsushima, Kenji; Saito, Yoshinobu; Abe, Mitsuhiro; Horimasu, Yasushi; Kashiwada, Takeru; Mori, Kazuhiko; Sato, Motonobu; Nishiya, Takayoshi; Takamatsu, Kazuhiko; Sun, Yuchen; Arakawa, Noriaki; Izumi, Tohru; Ohno, Yasuo; Saito, Yoshiro; Hanaoka, Masayuki

doi:10.1038/s41598-022-24406-z

Cited by 8 publications

(6 citation statements)

References 45 publications

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“…Similar to the biomarkers identified in this study, we have reported that plasma LPC(14:0) levels can be used as a biomarker for discriminating DILD from IIPs and CTD [ 19 ]. However, the drawbacks of LPC(14:0) in the differential diagnosis of DILD include that its plasma concentration also changes in patients with BP.…”

Section: Discussionsupporting

confidence: 70%

“…The metabolomic profile also provides a comprehensive readout of individual responses to treatment, which may enhance the discovery of biomarkers for the efficacy and adverse effects of drugs [ 18 ]. Indeed, several new biomarkers (lysophosphatidylcholines [LPCs]) for DILD were identified in our previous metabolomic study focusing on lipids [ 19 ], which showed that LPCs distinguish DILD from IIPs and CTD, but decreased plasma concentrations of LPCs can be observed not only in patients with acute DILD but also those with bacterial pneumonia (BP) [ 19 ]. Thus, a novel biomarker specific to DILD needs to be explored.…”

Section: Introductionmentioning

confidence: 99%

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Identification of kynurenine and quinolinic acid as promising serum biomarkers for drug-induced interstitial lung diseases

Sun,

Saito,

Ushiki

et al. 2024

Respir Res

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Background Drug-induced interstitial lung disease (DILD) is a lung injury caused by various types of drugs and is a serious problem in both clinical practice and drug development. Clinical management of the condition would be improved if there were DILD-specific biomarkers available; this study aimed to meet that need. Methods Biomarker candidates were identified by non-targeted metabolomics focusing on hydrophilic molecules, and further validated by targeted approaches using the serum of acute DILD patients, DILD recovery patients, DILD-tolerant patients, patients with other related lung diseases, and healthy controls. Results Serum levels of kynurenine and quinolinic acid (and kynurenine/tryptophan ratio) were elevated significantly and specifically in acute DILD patients. The diagnostic potentials of these biomarkers were superior to those of conventional lung injury biomarkers, Krebs von den Lungen-6 and surfactant protein-D, in discriminating between acute DILD patients and patients with other lung diseases, including idiopathic interstitial pneumonia and lung diseases associated with connective tissue diseases. In addition to identifying and evaluating the biomarkers, our data showed that kynurenine/tryptophan ratios (an indicator of kynurenine pathway activation) were positively correlated with serum C-reactive protein concentrations in patients with DILD, suggesting the potential association between the generation of these biomarkers and inflammation. Our in vitro experiments demonstrated that macrophage differentiation and inflammatory stimulations typified by interferon gamma could activate the kynurenine pathway, resulting in enhanced kynurenine levels in the extracellular space in macrophage-like cell lines or lung endothelial cells. Extracellular quinolinic acid levels were elevated only in macrophage-like cells but not endothelial cells owing to the lower expression levels of metabolic enzymes converting kynurenine to quinolinic acid. These findings provide clues about the molecular mechanisms behind their specific elevation in the serum of acute DILD patients. Conclusions The serum concentrations of kynurenine and quinolinic acid as well as kynurenine/tryptophan ratios are promising and specific biomarkers for detecting and monitoring DILD and its recovery, which could facilitate accurate decisions for appropriate clinical management of patients with DILD.

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Section: Discussionsupporting

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Identification of kynurenine and quinolinic acid as promising serum biomarkers for drug-induced interstitial lung diseases

Sun,

Saito,

Ushiki

et al. 2024

Respir Res

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“…One more example is inflammation induced by drug exposure, which has an effect on LPC concentrations. In a recent study, LPCs were reported as potential biomarkers for drug-induced interstitial lung disease [ 84 ]. The selected biomarkers showed no associations with other drugs and were effectively implemented to differentiate between other lung diseases: idiopathic interstitial pneumonia and lung disease associated with connective tissue disease.…”

Section: Research Field Landscapementioning

confidence: 99%

Advances in Mass Spectrometry-Based Blood Metabolomics Profiling for Non-Cancer Diseases: A Comprehensive Review

Demicheva,

Dordiuk,

Polanco Espino

et al. 2024

Metabolites

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Blood metabolomics profiling using mass spectrometry has emerged as a powerful approach for investigating non-cancer diseases and understanding their underlying metabolic alterations. Blood, as a readily accessible physiological fluid, contains a diverse repertoire of metabolites derived from various physiological systems. Mass spectrometry offers a universal and precise analytical platform for the comprehensive analysis of blood metabolites, encompassing proteins, lipids, peptides, glycans, and immunoglobulins. In this comprehensive review, we present an overview of the research landscape in mass spectrometry-based blood metabolomics profiling. While the field of metabolomics research is primarily focused on cancer, this review specifically highlights studies related to non-cancer diseases, aiming to bring attention to valuable research that often remains overshadowed. Employing natural language processing methods, we processed 507 articles to provide insights into the application of metabolomic studies for specific diseases and physiological systems. The review encompasses a wide range of non-cancer diseases, with emphasis on cardiovascular disease, reproductive disease, diabetes, inflammation, and immunodeficiency states. By analyzing blood samples, researchers gain valuable insights into the metabolic perturbations associated with these diseases, potentially leading to the identification of novel biomarkers and the development of personalized therapeutic approaches. Furthermore, we provide a comprehensive overview of various mass spectrometry approaches utilized in blood metabolomics research, including GC-MS, LC-MS, and others discussing their advantages and limitations. To enhance the scope, we propose including recent review articles supporting the applicability of GC×GC-MS for metabolomics-based studies. This addition will contribute to a more exhaustive understanding of the available analytical techniques. The Integration of mass spectrometry-based blood profiling into clinical practice holds promise for improving disease diagnosis, treatment monitoring, and patient outcomes. By unraveling the complex metabolic alterations associated with non-cancer diseases, researchers and healthcare professionals can pave the way for precision medicine and personalized therapeutic interventions. Continuous advancements in mass spectrometry technology and data analysis methods will further enhance the potential of blood metabolomics profiling in non-cancer diseases, facilitating its translation from the laboratory to routine clinical application.

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“…14,15 Notably, lipids are considered appropriate targets for biomarker development. 16 Consequently, there is a rising interest in employing lipidomics to discover appropriate biomarkers for clinical application, identify novel targets for therapeutic intervention in disease progression, and unravel the underlying molecular mechanisms involved. 17 Due to practical and ethical concerns, very limited experiments can be conducted on human subjects; animal models spanning from non-mammalian models to non-human primates (NHPs) remain indispensable for the pharmacological testing and elucidation of the mechanism of T2DM.…”

Section: Introductionmentioning

confidence: 99%

“…Mass spectrometry (MS)‐based lipidomics can be conducted through untargeted and targeted fashion, each with their own distinct features, and a combination of these two approaches is often utilized to maximize the coverage of lipid species detected and quantified in complex biological samples 14,15 . Notably, lipids are considered appropriate targets for biomarker development 16 . Consequently, there is a rising interest in employing lipidomics to discover appropriate biomarkers for clinical application, identify novel targets for therapeutic intervention in disease progression, and unravel the underlying molecular mechanisms involved 17 …”

Section: Introductionmentioning

confidence: 99%

Combined untargeted and targeted lipidomics approaches reveal potential biomarkers in type 2 diabetes mellitus cynomolgus monkeys

Tian,

Yang,

et al. 2023

J of Medical Primatology

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BackgroundThe significantly increasing incidence of type 2 diabetes mellitus (T2DM) over the last few decades triggers the demands of T2DM animal models to explore the pathogenesis, prevention, and therapy of the disease. The altered lipid metabolism may play an important role in the pathogenesis and progression of T2DM. However, the characterization of molecular lipid species in fasting serum related to T2DM cynomolgus monkeys is still underrecognized.MethodsUntargeted and targeted LC–mass spectrometry (MS)/MS‐based lipidomics approaches were applied to characterize and compare the fasting serum lipidomic profiles of T2DM cynomolgus monkeys and the healthy controls.ResultsMultivariate analysis revealed that 196 and 64 lipid molecules differentially expressed in serum samples using untargeted and targeted lipidomics as the comparison between the disease group and healthy group, respectively. Furthermore, the comparative analysis of differential serum lipid metabolites obtained by untargeted and targeted lipidomics approaches, four common serum lipid species (phosphatidylcholine [18:0_22:4], lysophosphatidylcholine [14:0], phosphatidylethanolamine [PE] [16:1_18:2], and PE [18:0_22:4]) were identified as potential biomarkers and all of which were found to be downregulated. By analyzing the metabolic pathway, glycerophospholipid metabolism was associated with the pathogenesis of T2DM cynomolgus monkeys.ConclusionThe study found that four downregulated serum lipid species could serve as novel potential biomarkers of T2DM cynomolgus monkeys. Glycerophospholipid metabolism was filtered out as the potential therapeutic target pathway of T2DM progression. Our results showed that the identified biomarkers may offer a novel tool for tracking disease progression and response to therapeutic interventions.

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Identification and characterization of lysophosphatidylcholine 14:0 as a biomarker for drug-induced lung disease

Cited by 8 publications

References 45 publications

Identification of kynurenine and quinolinic acid as promising serum biomarkers for drug-induced interstitial lung diseases

Identification of kynurenine and quinolinic acid as promising serum biomarkers for drug-induced interstitial lung diseases

Advances in Mass Spectrometry-Based Blood Metabolomics Profiling for Non-Cancer Diseases: A Comprehensive Review

Combined untargeted and targeted lipidomics approaches reveal potential biomarkers in type 2 diabetes mellitus cynomolgus monkeys

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