title: Magic angle spinning NMR-based metabolic profiling of head and neck squamous cell carcinoma tissues.
abstract: High-resolution magic-angle spinning (HR-MAS) proton NMR spectroscopy is used to explore the metabolic signatures of head and neck squamous cell carcinoma (HNSCC) which included matched normal adjacent tissue (NAT) and tumor originating from tongue, lip, larynx and oral cavity, and associated lymph-node metastatic (LN-Met) tissues. A total of 43 tissues (18 NAT, 18 Tumor and 7 LN-Met) from 22 HNSCC patients were analyzed. Principal Component Analysis of NMR data showed a clear classification between NAT and tumor tissues, however, LN-Met tissues were classified among tumor. A partial least-squares discriminant analysis model generated from NMR metabolic profiles was used to differentiate normal from tumor samples (Q(2) > 0.80, Receiver Operator Characteristic area under the curve >0.86, using 7-fold cross validation). HNSCC and LN-Met tissues showed elevated levels of lactate, amino acids including leucine, isoleucine, valine, alanine, glutamine, glutamate, aspartate, glycine, phenylalanine and tyrosine, choline containing compounds, creatine, taurine, glutathione, and decreased levels of triglycerides. These elevated metabolites were associated with highly active glycolysis, increased amino acids influx (anaplerosis) into the TCA cycle, altered energy metabolism, membrane choline phospholipid metabolism, and oxidative and osmotic defense mechanisms. Moreover, decreased levels of triglycerides may indicate lipolysis followed by β-oxidation of fatty acids that may exist to deliver bioenergy for rapid tumor cell proliferation and growth.
authors.affiliation: Department of Chemistry and Biophysics, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Bagganahalli S
authors.initials: BS
authors.lastname: Somashekar
authors.forename: Pachiyappan
authors.initials: P
authors.lastname: Kamarajan
authors.forename: Theodora
authors.initials: T
authors.lastname: Danciu
authors.forename: Yvonne L
authors.initials: YL
authors.lastname: Kapila
authors.forename: Arul M
authors.initials: AM
authors.lastname: Chinnaiyan
authors.forename: Thekkelnaycke M
authors.initials: TM
authors.lastname: Rajendiran
authors.forename: Ayyalusamy
authors.initials: A
authors.lastname: Ramamoorthy
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000596:Amino Acids / Q000378:metabolism; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006019:Glycolysis; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D050356:Lipid Metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D012372:ROC Curve
chemical_list: D000596:Amino Acids; D014408:Biomarkers, Tumor