Department of Surgery and Cancer, Imperial College London, 10th Floor, QEQM Wing, St Mary's Hospital, London W2 1NY, UK.
Eur J Cancer. 2013 Nov;49(17):3625-37. doi: 10.1016/j.ejca.2013.07.004. Epub 2013 Jul 26.
This review aims to identify metabolomic biomarkers of oesophago-gastric (OG) cancer in human biological samples, and to discuss the dominant metabolic pathways associated with the observed changes.
A systematic review of the literature, up to and including 9th November 2012, was conducted for experimental studies investigating the metabolomic profile of human biological samples from patients with OG cancer compared to a control group. Inclusion criteria for analytical platforms were mass spectrometry or nuclear magnetic resonance spectroscopy. The QUADAS-2 tool was used to assess the quality of the included studies.
Twenty studies met the inclusion criteria and samples utilised for metabolomic analysis included tissue (n = 11), serum (n = 8), urine (n = 1) and gastric content (n = 1). Several metabolites of glycolysis, the tricarboxylic acid cycle, anaerobic respiration and protein/lipid metabolism were found to be significantly different between cancer and control samples. Lactate and fumurate were the most commonly recognised biomarkers of OG cancer related to cellular respiration. Valine, glutamine and glutamate were the most commonly identified amino acid biomarkers. Products of lipid metabolism including saturated and un-saturated free fatty acids, ketones and aldehydes and triacylglycerides were also identified as biomarkers of OG cancer. Unclear risk of bias for patient selection was reported for the majority of studies due to the lack of clarity regarding patient recruitment.
The application of metabolomics for biomarker detection in OG cancer presents new opportunities for the purposes of screening and therapeutic monitoring. Future studies should provide clear details of patient selection and develop metabolite assays suitable for progress beyond phase 1 pre-clinical exploratory studies.
本综述旨在鉴定人生物样本中食管胃（OG）癌症的代谢组学生物标志物，并讨论与观察到的变化相关的主要代谢途径。
对截至 2012 年 11 月 9 日的实验研究进行了系统的文献回顾，这些研究调查了与对照组相比，OG 癌症患者人生物样本的代谢组学特征。分析平台的纳入标准为质谱或核磁共振波谱。使用 QUADAS-2 工具评估纳入研究的质量。
有 20 项研究符合纳入标准，用于代谢组学分析的样本包括组织（n=11）、血清（n=8）、尿液（n=1）和胃内容物（n=1）。在癌症和对照样本之间，几种糖酵解、三羧酸循环、无氧呼吸和蛋白质/脂质代谢的代谢物被发现有明显差异。乳酸和富马酸是与细胞呼吸有关的 OG 癌症最常见的生物标志物。缬氨酸、谷氨酰胺和谷氨酸是最常见的氨基酸生物标志物。脂质代谢产物，包括饱和和不饱和游离脂肪酸、酮和醛以及三酰基甘油，也被鉴定为 OG 癌症的生物标志物。由于缺乏对患者招募的明确说明，大多数研究对患者选择的偏倚风险评估不清。
代谢组学在 OG 癌症生物标志物检测中的应用为筛查和治疗监测提供了新的机会。未来的研究应提供患者选择的明确细节，并开发适合超越 1 期临床前探索性研究阶段的代谢物检测方法。
