D-mannose: a novel prognostic biomarker for patients with esophageal adenocarcinoma

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Metabolomic profiling is a promising approach to identify new biomarkers for cancer prognosis. However, the role of circulating metabolites as prognostic indicators in esophageal adenocarcinoma (EAC) has not been well explored. In this study, we aimed to evaluate the prognostic value of three serum metabolites, <span style="text-transform:lowercase;font-variant:small-caps;">d</span>-mannose, <span style="text-transform:lowercase;font-variant:small-caps;">l</span>-proline (LP), and 3-hydroxybutyrate (BHBA), which were significantly different between EAC patients and controls, identified through a global and targeted metabolite profiling. We measured the levels of <span style="text-transform:lowercase;font-variant:small-caps;">d</span>-mannose, LP, and BHBA in pretreatment serum from 159 EAC patients, using liquid chromatography–mass spectrometry/mass spectrometry (LC-MS/MS) methods. A multivariable Cox model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association of these metabolites with recurrence and overall survival. We found that serum levels of <span style="text-transform:lowercase;font-variant:small-caps;">d</span>-mannose were significantly associated with recurrence and overall survival in EAC patients, whereas levels of LP and BHBA were not. Compared with patients with a low (first tertile) level of <span style="text-transform:lowercase;font-variant:small-caps;">d</span>-mannose, those with a high (second plus third tertiles) level had 49% reduced risk of recurrence (HR = 0.51; 95% CI: 0.29–0.91; <span style="font-style:italic;">P</span> = 0.02), and 56% reduced risk of death (HR = 0.44; 95% CI: 0.25–0.77, <span style="font-style:italic;">P</span> < 0.01). The significant association of high <span style="text-transform:lowercase;font-variant:small-caps;">d</span>-mannose levels with better prognosis was consistent among patients with early-stage and advanced-stage EAC. Our results suggest that serum level of <span style="text-transform:lowercase;font-variant:small-caps;">d</span>-mannose may be used as a novel prognostic biomarker for patients with EAC. Further studies in independent populations are warranted to confirm our findings.</span>

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