Identification of hypoxanthine and phosphoenolpyruvic acid as serum markers associated with chemoradiotherapy response in locally advanced rectal cancer.

Abstract

507 Background: Patients show variable responses to chemoradiotherapy (CRT), generally performed before surgery for locally advanced rectal cancer (LARC). We aimed to identify molecular markers predictive of CRT responses by analyzing low-mass ions (LMIs) in serum of LARC patients. Methods: LMIs (<1000 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. The HX concentration was higher in patients with ypStage 0-I compared with ypStage II-IV (p = 0.034) or ypStage III-IV (p = 0.030); a similar difference was observed between TRG IV-III and TRG 1 (p = 0.035). In contrast, the concentration of PEP was significantly lower in TRG 4-3 compared to TRG 2-1 (p = 0.012), and a lower PEP level was also found in ypStage 0 compared to ypStage I-IV, with marginal significance (p = 0.061). Conclusions: This study demonstrated that pretreatment serum concentrations of HX and PEP, identified using LMI profiling, may be useful for predicting the CRT response of LARC.