High tumor glycine concentration is an adverse prognostic factor in locally advanced rectal cancer

Abstract

Background and purpose: 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).

Materials and 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.

Keywords: Glycine; Metabolism; Metastasis; Radiotherapy; Rectal cancer; Survival.