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Cholesterol and its esters as serum biomarkers in malignant obstructive jaundice: a single step 1H NMR metabolomic approach

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Abstract

The paucity of biomarkers for malignant obstructive jaundice results in formidable morbidity and mortality rates. Therefore, alternative diagnostic measures are required for improved clinical interpretation and better peri-operative management of patients. In the present study, 1H NMR-based metabolomic approach has been applied to investigate serum and bile based metabolic biomarkers in benign and malignant causes of obstructive jaundice (OBJ). Serum and bile specimens from benign OBJ patients (n = 28), malignant OBJ patients (n = 36) and serum of healthy controls (n = 57) were analysed by 1H NMR spectroscopy. Quantitation of eight serum metabolites (isobutyrate, lactate, alanine, acetone, glutamine, creatine, threonine and 1-methylhistidine) was carried out. A newer and rapid single step NMR based semi-quantitative ratio analysis of serum total cholesterol (tCho), cholesterol (Chol) and cholesterol ester (CE) were performed in deuterated dimethyl sulfoxide-d6. In bile, total bile acids, cholesterol, phosphatidylcholine, glycerophosphatidylcholine and urea were quantified. The effect of benign and malignant OBJ on small metabolites and lipids were statistically analysed by Mann–Whitney U test and multivariate discriminant function analysis. It was found that malignancy could be differentiated from benign cases of OBJ with a correct classification of 85.7 % when eight serum metabolites in combination with ratios of serum cholesterol were analysed. Significant alterations in serum tCho, Chol, CE and serum metabolites may have potential for early and differential non-invasive diagnosis of malignant and benign OBJ cases. It will further augment the novel insights of local and systemic effects in OBJ patients.

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Abbreviations

OBJ:

Obstructive jaundice

Chol:

Cholesterol

CE:

Cholesterol esters

tCho:

Total cholesterol

PtdCho:

Phosphatidyl choline

DFA:

Discriminant function analysis

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Acknowledgments

The authors gratefully acknowledge Council of Scientific and Industrial Research (CSIR), New Delhi for providing fellowship to SS. Authors thank Ms. Richa Sharma, Department of Nephrology, for her fruitful suggestions during manuscript preparation. We are grateful to Dr. S. K. Mandal, bio-statistician, Centre of Biomedical Magnetic Resonance for his fruitful suggestion in multivariate statistical analysis.

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Authors and Affiliations

  1. Centre of Biomedical Magnetic Resonance, Sanjay Gandhi Post-Graduate Institute of Medical Sciences Campus, Raibarely Road, Lucknow, 226014, Uttar Pradesh, India

    Shatakshi Srivastava & Raja Roy

  2. Department of General Surgery, King George’s Medical University, Lucknow, 226014, Uttar Pradesh, India

    Santosh Kumar, Hari Om Gupta, Devendra Singh, Jitendra Kumar Kushwaha & Abhinav Arun Sonkar

  3. Department of Surgical Gastroenterology, King George’s Medical University, Lucknow, 226014, Uttar Pradesh, India

    Abhijit Chandra

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  1. Shatakshi Srivastava
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  2. Raja Roy
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  3. Santosh Kumar
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  4. Hari Om Gupta
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Correspondence to Raja Roy or Abhinav Arun Sonkar.

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Srivastava, S., Roy, R., Kumar, S. et al. Cholesterol and its esters as serum biomarkers in malignant obstructive jaundice: a single step 1H NMR metabolomic approach. Metabolomics 9, 1181–1191 (2013). https://doi.org/10.1007/s11306-013-0533-x

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