Gu Jianchun, Liang Dong, Pierzynski Jeanne A, Zheng Leizhen, Ye Yuanqing, Zhang Jinhua, Ajani Jaffer A, Wu Xifeng
Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Department of Oncology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.
Carcinogenesis. 2017 Feb 1;38(2):162-167. doi: 10.1093/carcin/bgw207.
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, d-mannose, l-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 d-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 d-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 d-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; P = 0.02), and 56% reduced risk of death (HR = 0.44; 95% CI: 0.25-0.77, P < 0.01). The significant association of high d-mannose levels with better prognosis was consistent among patients with early-stage and advanced-stage EAC. Our results suggest that serum level of d-mannose may be used as a novel prognostic biomarker for patients with EAC. Further studies in independent populations are warranted to confirm our findings.
代谢组学分析是一种很有前景的方法，可用于识别癌症预后的新生物标志物。然而，循环代谢物作为食管腺癌（EAC）预后指标的作用尚未得到充分研究。在本研究中，我们旨在评估三种血清代谢物——D-甘露糖、L-脯氨酸（LP）和3-羟基丁酸（BHBA）的预后价值，这些代谢物在EAC患者和对照组之间存在显著差异，是通过全代谢组和靶向代谢物分析确定的。我们使用液相色谱-质谱/质谱（LC-MS/MS）方法，测量了159例EAC患者预处理血清中D-甘露糖、LP和BHBA的水平。采用多变量Cox模型估计这些代谢物与复发和总生存关联的风险比（HR）和95%置信区间（95%CI）。我们发现，EAC患者血清中D-甘露糖水平与复发和总生存显著相关，而LP和BHBA水平则不然。与D-甘露糖水平低（第一三分位数）的患者相比，水平高（第二和第三三分位数）的患者复发风险降低49%（HR = 0.51；95%CI：0.29 - 0.91；P = 0.02），死亡风险降低56%（HR = 0.44；95%CI：0.25 - 0.77，P < 0.01）。在早期和晚期EAC患者中，高D-甘露糖水平与更好预后的显著关联是一致的。我们的结果表明，血清D-甘露糖水平可能作为EAC患者一种新的预后生物标志物。有必要在独立人群中进行进一步研究以证实我们的发现。
