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Large Scale Non-targeted Metabolomic Profiling of Serum by Ultra Performance Liquid Chromatography-Mass Spectrometry UPLC-MS
Published on: March 14, 2013
Discrimination of serum metabolomics profiles in infants with sepsis, based on liquid chromatography-mass
Li Wang1,2, Xinyi Cha2, Zhongxiao Zhang3
1Clinic and Research Center of Tuberculosis, Shanghai Pulmonary Hospital, Institute for Advanced Study, Tongji University School of Medicine, Shanghai, China.
Insights
Early diagnosis of infant sepsis is crucial. This study identified serum metabolites, including prolylhydroxyproline, as potential biomarkers for early sepsis detection in infants, improving diagnostic accuracy.
Area of Science:
- Pediatric Infectious Diseases
- Metabolomics
- Biomarker Discovery
Background:
- Sepsis in infants presents with insidious onset and rapid progression, leading to high mortality rates.
- Sensitive and robust biomarkers are essential for early diagnosis of infant sepsis.
Purpose of the Study:
- To identify serum metabolic profiles and potential biomarkers for early diagnosis of infant sepsis.
- To investigate the association of differential metabolites with clinical parameters and inflammatory pathways.
Main Methods:
- Serum samples from 30 infants with sepsis and 30 controls were analyzed using liquid chromatography-mass spectrometry-based metabolomics.
- Multivariate statistical analysis and ROC curves were employed to identify differential metabolites and assess diagnostic value.
- Pathway and network analyses were conducted to understand the biological roles of identified metabolites.
Main Results:
- Six differential metabolites were identified, including phosphatidic acid, phosphatidyl ethanolamine, cytidine 5'-diphosphocholine, sphingomyelin, prolylhydroxyproline, and phosphorylcholine.
- Prolylhydroxyproline demonstrated potential diagnostic value (AUC=0.832), with a combined model achieving AUC=0.859.
- Differential metabolites were correlated with C-reactive protein (CRP) and procalcitonin (PCT) levels and linked to inflammatory and metabolic signaling pathways.
Conclusions:
- Serum metabolite profiling can aid in the early diagnosis of infant sepsis.
- Prolylhydroxyproline, phosphatidyl ethanolamine, and cytidine 5'-diphosphocholine are identified as potential biomarkers for infant sepsis.
- The findings provide insights into the metabolic dysregulation and inflammatory pathways involved in infant sepsis.
Abstract:
Sepsis is one of the most important problems to be addressed in pediatrics, characterized by insidious onset, rapid progression, and high rates of severe infection and even mortality. Biomarkers with high sensitivity and robustness are urgently required for the early diagnosis of infant sepsis. Serum metabolomic approaches based on liquid chromatography-mass spectrometry were used to analyze the samples from 30 infants with sepsis at an early stage and 30 infants with noninfectious diseases. Multivariate statistical analysis was used to screen for differential metabolites and ROC curves were generated to find potential biomarkers. Six metabolites, including phosphatidic acid (PA (8:0/14:0)), phosphatidyl ethanolamine (PE (16:0/18:2(9Z,12Z))), cytidine 5'-diphosphocholine (CDP-CHO), sphingomyelin (SM (d18:0/16:1(9Z))), prolylhydroxyproline and phosphorylcholine (P-CHO), were identified between the two groups. ROC curve analysis showed that prolylhydroxyproline (AUC = 0.832) had potential diagnostic values for infant sepsis. The AUC value was 0.859 (CI: 0.764, 0.954) in the combined model. Prolylhydroxyproline were found to be correlated with CRP and PCT levels, while PE and CDP-CHO associated with PCT levels. Pathway analysis indicated that glycerophospholipid metabolism, aminoacyl-tRNA biosynthesis and necroptosis pathways played important roles in infant sepsis. Network analysis showed that the differential metabolites were linked to ERK/ MAPK, NF-κB, AMPK, mTOR, and other classical inflammatory and metabolic signaling pathways. This study identified serum metabolite profiles and three metabolites as potential biomarkers in infants with sepsis. The findings will help improve the early diagnosis of sepsis in infants.
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