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Proton HR-MAS MR spectroscopy of oral squamous cell carcinoma tissues: an ex vivo study to identify malignancy induced metabolic fingerprints

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Abstract

Oral squamous cell carcinoma (SCC) represents more than 90% of all head and neck cancers as reported by Hermans (Cancer Imaging, 5(Spec No A), S52–S57, 2005), which draws attention of investigative research for novel predictive metabolic biomarkers to understand the malignancy induced biochemical perturbations occurring at molecular level. In the present work, proton HR-MAS NMR spectroscopic studies have been performed on resected human oral SCC tumor tissues, its neighboring margins and bed tissues (n = 159), obtained from 36 patients (n = 27 training set; n = 9 unknown test set), for the identification of metabolic fingerprints. The proton NMR spectra were then subjected to chemometric unsupervised PCA and supervised OSC-filtered PCA and PLS-DA multivariate analysis. Application of PLS-DA on orthogonally signal corrected training data-set (n = 120 tissue specimens; 27 patients) allowed >95% correct classification of malignant tissues from benign samples with >98% specificity and sensitivity. The OSC-PLS-DA model thus constructed was used to predict the class membership of unknown tissue specimens (n = 39) obtained from nine patients. These tissue samples were correctly predicted in its respective histological categories with 97.4% diagnostic accuracy. The regression coefficients obtained from OSC-filtered PLS-DA model indicated that malignant tissues had higher levels of glutamate, choline, phosphocholine, lactate, acetate, taurine, glycine, leucine, lysine, isoleucine and alanine, and lower levels of creatine and PUFA, representing altered metabolic processes (lipidogenesis, protein synthesis, and volume regulation) during tumor progression. Thus proton HR-MAS MR spectroscopy could efficiently identify the metabolic perturbations of malignant tumor from non-malignant bed and margins tissue specimens, which may be helpful in understanding the extent of tumor penetration in neighboring tissues.

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Abbreviations

HR-MAS:

High resolution magic angle spinning

PCA:

Principal component analysis

OSC:

Orthogonal signal correction

PLS:

Partial least square

NOESY:

Nuclear overhauser enhancement spectroscopy

COSY:

Correlation spectroscopy

CPMG:

Carr Purcell Meiboom Gill sequence

HSQC:

Heteronuclear single quantum coherence

SCC:

Squamous cell carcinoma

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Acknowledgments

The authors wish to acknowledge division of SAIF at Central Drug Research Institute (CDRI), Lucknow, for offering lab facilities to acquire NMR data. The Department of Science and Technology, New Delhi is thanked for providing SRF fellowship to Shatakshi Srivastava. The authors gratefully acknowledge Department of Science and Technology, New Delhi for providing a fellowship and NMR facility.

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Authors and Affiliations

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

    Shatakshi Srivastava & Raja Roy

  2. Departments of General Surgery, Chattrapati Shahuji Maharaj Medical University, Lucknow, 226001, Uttar Pradesh, India

    Vivek Gupta, Ashish Tiwari & Abhinav A. Sonkar

  3. Departments of Pathology, Chattrapati Shahuji Maharaj Medical University, Lucknow, India

    Anand N. Srivastava

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  1. Shatakshi Srivastava
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  2. Raja Roy
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  3. Vivek Gupta
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  4. Ashish Tiwari
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  5. Anand N. Srivastava
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  6. Abhinav A. Sonkar
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Correspondence to Raja Roy or Abhinav A. Sonkar.

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Srivastava, S., Roy, R., Gupta, V. et al. Proton HR-MAS MR spectroscopy of oral squamous cell carcinoma tissues: an ex vivo study to identify malignancy induced metabolic fingerprints. Metabolomics 7, 278–288 (2011). https://doi.org/10.1007/s11306-010-0253-4

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  • DOI: https://doi.org/10.1007/s11306-010-0253-4

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