title: High tumor glycine concentration is an adverse prognostic factor in locally advanced rectal cancer.
abstract: OBJECTIVE
  Recognizing the link between altered tumor metabolism and disease aggressiveness, this study aimed to identify associations between tumor metabolic profiles and therapeutic outcome in locally advanced rectal cancer (LARC).
  
  
  METHODS
  Pretreatment tumor metabolic profiles from 54 LARC patients receiving combined-modality neoadjuvant treatment and surgery were acquired by high-resolution magic angle spinning magnetic resonance spectroscopy (HR MAS MRS). Metabolite concentrations were correlated to TNM and the presence of disseminated tumor cells (DTC) at diagnosis, ypTN and tumor regression grade (TRG) following neoadjuvant treatment, and progression-free survival (PFS).
  
  
  RESULTS
  Pretreatment tumor metabolite concentrations showed no significant associations to TNM, DTC, ypTN or TRG. In univariate regression analysis, high concentrations of glycine, creatine and myo-inositol were significantly associated with poor PFS, with metastasis as main PFS event. In multivariate analysis, high glycine concentration remained most significantly associated with poor PFS (hazard ratio=4.4, 95% confidence interval=1.4-14.3, p=0.008).
  
  
  CONCLUSIONS
  High tumor glycine concentration was identified as adverse prognostic factor for PFS in LARC. In a patient population treated with curative intent but with metastatic disease as main PFS event further investigations of glycine as early predictor of metastatic progression and therapeutic target are warranted.
authors.affiliation: Department of Oncology, Akershus University Hospital, Lørenskog, Norway. Electronic address: k.r.redalen@medisin.uio.no.
authors.forename: Kathrine Røe
authors.initials: KR
authors.lastname: Redalen
authors.affiliation: Department of Health Science, Sør-Trøndelag University College, Trondheim, Norway; Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Beathe
authors.initials: B
authors.lastname: Sitter
authors.affiliation: Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Tone Frost
authors.initials: TF
authors.lastname: Bathen
authors.affiliation: Department of Pathology, Oslo University Hospital, Norway.
authors.forename: Krystyna K
authors.initials: KK
authors.lastname: Grøholt
authors.affiliation: Department of Radiology and Nuclear Medicine, Oslo University Hospital, Norway.
authors.forename: Knut Håkon
authors.initials: KH
authors.lastname: Hole
authors.affiliation: Department of Oncology, Oslo University Hospital, Norway.
authors.forename: Svein
authors.initials: S
authors.lastname: Dueland
authors.affiliation: Department of Gastroenterological Surgery, Oslo University Hospital, Norway; Department of Tumor Biology, Oslo University Hospital, Norway; Institute of Clinical Medicine, University of Oslo, Norway.
authors.forename: Kjersti
authors.initials: K
authors.lastname: Flatmark
authors.affiliation: Department of Oncology, Akershus University Hospital, Lørenskog, Norway; Institute of Clinical Medicine, University of Oslo, Norway.
authors.forename: Anne Hansen
authors.initials: AH
authors.lastname: Ree
authors.affiliation: Department of Radiology and Nuclear Medicine, Oslo University Hospital, Norway.
authors.forename: Therese
authors.initials: T
authors.lastname: Seierstad
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D005998:Glycine / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D055442:Metabolome; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011379:Prognosis; D012004:Rectal Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D005998:Glycine
keywords: Glycine; Metabolism; Metastasis; Radiotherapy; Rectal cancer; Survival