Identification of Hypoxanthine and Phosphoenolpyruvic Acid as Serum Markers of Chemoradiotherapy Response in Locally Advanced Rectal Cancer
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Purpose Patients show variable responses to chemoradiotherapy (CRT), which is generally administeredbefore surgery for locally advanced rectal cancer (LARC). The aim of this study was toidentify molecular markers predictive of CRT responses by analysis of low-mass ions (LMIs)in serum of LARC patients. Materials and MethodsLMIs (< 1,000 m/z) in serum obtained before CRT from 73 LARC (cT3-4) patients wereprofiled using matrix-assisted laser desorption/ionization mass spectrometry. LMIs withhigher weighting factors in discriminating CRT responses were selected using principalcomponents analysis and discriminant analysis. Selected LMIs were identified using theHuman Metabolome Database. The concentrations of identified LMIs were determined bycolorimetric enzyme assay, and compared according to post-CRT pathological stage(ypStage) or Dworak’s tumor regression grade (TRG). ResultsThe nine highest-ranking LMIs were selected. Among them, two LMIs with 137.08 and169.04 m/z were identified as hypoxanthine (HX) and phosphoenolpyruvic acid (PEP),respectively. Higher HX concentration was observed in patients with ypStage 0-1 comparedto ypStage 2-4 (p=0.034) or ypStage 3-4 (p=0.030); a similar difference was observedbetween TRG 4-3 and TRG 1 (p=0.035). HX > 16.0 μM showed significant association withypStage 0-1 or TRG 4-3 than ypStage 3-4 (p=0.009) or TRG 1 (p=0.024), respectively. Incontrast, a significantly lower concentration of PEP was observed in TRG 4-3 compared withTRG 2-1 (p=0.012). ConclusionFindings of this study demonstrated that serum concentrations of HX and PEP, identifiedusing LMI profiling, may be useful for predicting the CRT response of LARC patients beforetreatment.
Abstract
Purpose Patients show variable responses to chemoradiotherapy (CRT), which is generally administeredbefore surgery for locally advanced rectal cancer (LARC). The aim of this study was toidentify molecular markers predictive of CRT responses by analysis of low-mass ions (LMIs)in serum of LARC patients. Materials and MethodsLMIs (< 1,000 m/z) in serum obtained before CRT from 73 LARC (cT3-4) patients wereprofiled using matrix-assisted laser desorption/ionization mass spectrometry. LMIs withhigher weighting factors in discriminating CRT responses were selected using principalcomponents analysis and discriminant analysis. Selected LMIs were identified using theHuman Metabolome Database. The concentrations of identified LMIs were determined bycolorimetric enzyme assay, and compared according to post-CRT pathological stage(ypStage) or Dworak’s tumor regression grade (TRG). ResultsThe nine highest-ranking LMIs were selected. Among them, two LMIs with 137.08 and169.04 m/z were identified as hypoxanthine (HX) and phosphoenolpyruvic acid (PEP),respectively. Higher HX concentration was observed in patients with ypStage 0-1 comparedto ypStage 2-4 (p=0.034) or ypStage 3-4 (p=0.030); a similar difference was observedbetween TRG 4-3 and TRG 1 (p=0.035). HX > 16.0 μM showed significant association withypStage 0-1 or TRG 4-3 than ypStage 3-4 (p=0.009) or TRG 1 (p=0.024), respectively. Incontrast, a significantly lower concentration of PEP was observed in TRG 4-3 compared withTRG 2-1 (p=0.012). ConclusionFindings of this study demonstrated that serum concentrations of HX and PEP, identifiedusing LMI profiling, may be useful for predicting the CRT response of LARC patients beforetreatment.
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