Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom.
Department of Radiation Oncology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
Cancer Epidemiol Biomarkers Prev. 2022 Jul 1;31(7):1261-1274. doi: 10.1158/1055-9965.EPI-21-0687.
This review aims to develop an appropriate review tool for systematically collating metabolites that are dysregulated in disease and applies the method to identify novel diagnostic biomarkers for hepatocellular carcinoma (HCC). Studies that analyzed metabolites in blood or urine samples where HCC was compared with comparison groups (healthy, precirrhotic liver disease, cirrhosis) were eligible. Tumor tissue was included to help differentiate primary and secondary biomarkers. Searches were conducted on Medline and EMBASE. A bespoke "risk of bias" tool for metabolomic studies was developed adjusting for analytic quality. Discriminant metabolites for each sample type were ranked using a weighted score accounting for the direction and extent of change and the risk of bias of the reporting publication. A total of 84 eligible studies were included in the review (54 blood, 9 urine, and 15 tissue), with six studying multiple sample types. High-ranking metabolites, based on their weighted score, comprised energy metabolites, bile acids, acylcarnitines, and lysophosphocholines. This new review tool addresses an unmet need for incorporating quality of study design and analysis to overcome the gaps in standardization of reporting of metabolomic data. Validation studies, standardized study designs, and publications meeting minimal reporting standards are crucial for advancing the field beyond exploratory studies.
本综述旨在开发一种合适的综述工具，用于系统地整理疾病中失调的代谢物，并将该方法应用于鉴定肝细胞癌（HCC）的新型诊断生物标志物。有资格纳入的研究分析了血液或尿液样本中的代谢物，其中 HCC 与对照组（健康、肝硬化前期肝病、肝硬化）进行了比较。纳入肿瘤组织有助于区分原发性和继发性生物标志物。在 Medline 和 EMBASE 上进行了检索。针对代谢组学研究开发了一种定制的“偏倚风险”工具，以调整分析质量。使用加权评分对每种样本类型的判别代谢物进行排序，评分考虑了报告出版物的报告方向和变化程度以及偏倚风险。共有 84 项符合条件的研究纳入综述（54 项血液、9 项尿液和 15 项组织），其中 6 项研究了多种样本类型。基于加权评分的高排名代谢物包括能量代谢物、胆汁酸、酰基辅酶 A 和溶血磷脂胆碱。这种新的综述工具满足了将研究设计和分析质量纳入其中的需求，以克服代谢组学数据报告标准化方面的差距。验证研究、标准化研究设计和符合最低报告标准的出版物对于推动该领域超越探索性研究至关重要。
