title: Identification of hypoxanthine and phosphoenolpyruvic Acid as serum markers of chemoradiotherapy response in locally advanced rectal cancer.
abstract: OBJECTIVE
  Patients show variable responses to chemoradiotherapy (CRT), which is generally administered before surgery for locally advanced rectal cancer (LARC). The aim of this study was to identify molecular markers predictive of CRT responses by analysis of low-mass ions (LMIs) in serum of LARC patients.
  
  
  METHODS
  LMIs (< 1,000 m/z) in serum obtained before CRT from 73 LARC (cT3-4) patients were profiled using matrix-assisted laser desorption/ionization mass spectrometry. LMIs with higher weighting factors in discriminating CRT responses were selected using principal components analysis and discriminant analysis. Selected LMIs were identified using the Human Metabolome Database. The concentrations of identified LMIs were determined by colorimetric enzyme assay, and compared according to post-CRT pathological stage (ypStage) or Dworak's tumor regression grade (TRG).
  
  
  RESULTS
  The nine highest-ranking LMIs were selected. Among them, two LMIs with 137.08 and 169.04 m/z were identified as hypoxanthine (HX) and phosphoenolpyruvic acid (PEP), respectively. Higher HX concentration was observed in patients with ypStage 0-1 compared to ypStage 2-4 (p=0.034) or ypStage 3-4 (p=0.030); a similar difference was observed between TRG 4-3 and TRG 1 (p=0.035). HX > 16.0 μM showed significant association with ypStage 0-1 or TRG 4-3 than ypStage 3-4 (p=0.009) or TRG 1 (p=0.024), respectively. In contrast, a significantly lower concentration of PEP was observed in TRG 4-3 compared with TRG 2-1 (p=0.012).
  
  
  CONCLUSIONS
  Findings of this study demonstrated that serum concentrations of HX and PEP, identified using LMI profiling, may be useful for predicting the CRT response of LARC patients before treatment.
authors.affiliation: Laboratory of Cell Biology, Cancer Research Institute, Seoul National University, Seoul, Korea ; Colorectal Cancer Branch, Research Institute, National Cancer Center, Goyang, Korea.
authors.forename: Kun
authors.initials: K
authors.lastname: Kim
authors.affiliation: Department of Radiation Oncology, Soonchunhyang University College of Medicine, Cheonan, Korea.
authors.forename: Seung-Gu
authors.initials: SG
authors.lastname: Yeo
authors.affiliation: Colorectal Cancer Branch, Research Institute, National Cancer Center, Goyang, Korea.
authors.forename: Byong Chul
authors.initials: BC
authors.lastname: Yoo
keywords: Chemoradiotherapy; Hypoxanthine; Low-mass ions; Metabolite; Phosphoenolpyruvate; Rectal neoplasms