title: Proton NMR-based metabolite analyses of archived serial paired serum and urine samples from myeloma patients at different stages of disease activity identifies acetylcarnitine as a novel marker of active disease.
abstract: BACKGROUND
  Biomarker identification is becoming increasingly important for the development of personalized or stratified therapies. Metabolomics yields biomarkers indicative of phenotype that can be used to characterize transitions between health and disease, disease progression and therapeutic responses. The desire to reproducibly detect ever greater numbers of metabolites at ever diminishing levels has naturally nurtured advances in best practice for sample procurement, storage and analysis. Reciprocally, since many of the available extensive clinical archives were established prior to the metabolomics era and were not processed in such an 'ideal' fashion, considerable scepticism has arisen as to their value for metabolomic analysis. Here we have challenged that paradigm.
  
  
  METHODS
  We performed proton nuclear magnetic resonance spectroscopy-based metabolomics on blood serum and urine samples from 32 patients representative of a total cohort of 1970 multiple myeloma patients entered into the United Kingdom Medical Research Council Myeloma IX trial.
  
  
  RESULTS
  Using serial paired blood and urine samples we detected metabolite profiles that associated with diagnosis, post-treatment remission and disease progression. These studies identified carnitine and acetylcarnitine as novel potential biomarkers of active disease both at diagnosis and relapse and as a mediator of disease associated pathologies.
  
  
  CONCLUSIONS
  These findings show that samples conventionally processed and archived can provide useful metabolomic information that has important implications for understanding the biology of myeloma, discovering new therapies and identifying biomarkers potentially useful in deciding the choice and application of therapy.
authors: School of Cancer Sciences, The University of Birmingham, Birmingham, United Kingdom. alessia@austin.utexas.edu
authors: Alessia
authors: A
authors: Lodi
authors: Stefano
authors: S
authors: Tiziani
authors: Farhat L
authors: FL
authors: Khanim
authors: Ulrich L
authors: UL
authors: Günther
authors: Mark R
authors: MR
authors: Viant
authors: Gareth J
authors: GJ
authors: Morgan
authors: Christopher M
authors: CM
authors: Bunce
authors: Mark T
authors: MT
authors: Drayson
mesh_terms: D000108:Acetylcarnitine / Q000097:blood* / Q000652:urine; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood* / Q000652:urine; D002331:Carnitine / Q000097:blood / Q000652:urine; D017326:Clinical Trials, Phase III as Topic; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055442:Metabolome; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009101:Multiple Myeloma / Q000097:blood* / Q000473:pathology / Q000628:therapy / Q000652:urine; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D000108:Acetylcarnitine; D002331:Carnitine