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Magic angle spinning NMR spectroscopic metabolic profiling of gall bladder tissues for differentiating malignant from benign disease

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Abstract

Gall bladder tissue specimens obtained from 112 patients were examined by high resolution magic angle spinning (HR-MAS) NMR spectroscopy. Fifty one metabolites were identified by combination of one and two-dimensional NMR spectra. To our knowledge, this is the first report on metabolic profiling of gall bladder tissues using HR-MAS NMR spectroscopy. Metabolic profiles were evaluated for differentiation between benign Chronic Cholecystitis (CC, n = 66) and xantho-granulomatous cholecystitis (XGC, n = 21) and malignant gall bladder cancer (GBC, n = 25). Increase in choline containing compounds, amino acids, taurine, nucleotides and lactate as common metabolites were observed in malignant tissues whereas lipid content was found low as compared to benign tissues. Principal component analysis obtained from the NMR data showed clear distinction between CC and GBC tissue specimens; however, 27 % of XGC tissues were classified with GBC. The partial least square discriminant analysis (PLS-DA) multivariate analysis between benign (CC, XGC) and malignant (GBC) on the training data set (CC; n = 51, XGC; n = 15, GBC; n = 19 tissues specimens) provided 100 % sensitivity and 94.12 % specificity. This PLS-DA model when executed on the spectra of unknown tissue specimens (CC; n = 15, XGC; n = 6, GBC; n = 6) classified them into the three histological categories with more than 95 % of diagnostic accuracy. Non-invasive in vivo MRS technique may be used in future to differentiate between benign (CC and XGC) and malignant (GBC) gall bladder diseases.

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Abbreviations

BCA:

Branch chain amino acids

CC:

Chronic cholecystitis

CPMG:

Carr-purcell-meiboom-gill

DQF-COSY:

Double quantum filtered-correlation spectroscopy

GBC:

Gall bladder cancer

HR-MAS:

High resolution-magic angle spinning

PLS-DA:

Partial least square regression discriminant analysis

PCA:

Principal component analysis

XGC:

Xantho-granulomatous cholecystitis

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Acknowledgments

Financial assistance from the Department of Science and Technology, Government of India is gratefully acknowledged. S. K. Bharti thanks Dr. K. Jayalakshmi Mulge and Ms Kanchan Sonkar for their help during the work.

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Authors and Affiliations

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

    Santosh Kumar Bharti & Raja Roy

  2. Department of Surgical Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raibarely Road, Lucknow, 226014, Uttar Pradesh, India

    Anu Behari & Vinay Kumar Kapoor

  3. Department of Pathology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

    Niraj Kumari & Narendra Krishnani

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  1. Santosh Kumar Bharti
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Bharti, S.K., Behari, A., Kapoor, V.K. et al. Magic angle spinning NMR spectroscopic metabolic profiling of gall bladder tissues for differentiating malignant from benign disease. Metabolomics 9, 101–118 (2013). https://doi.org/10.1007/s11306-012-0431-7

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