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

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.