Sanabria Juan R, Kombu Rajan S, Zhang Guo-Fang, Sandlers Yana, Ai Jizhou, Ibarra Rafael A, Abbas Rime, Goyal Kush, Brunengraber Henri
Department of Surgery, Case Western Reserve University School of Medicine, Cleveland, OH, USA; Department of Nutrition, Case Western Reserve University School of Medicine, Cleveland, OH, USA; Department of Preventive Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA; Department of Surgery and Research, Cancer Treatment Centers of America, Chicago, IL, USA; Department of Biostatistics, Cancer Treatment Centers of America, Chicago, IL, USA.
Department of Nutrition, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
HPB (Oxford). 2016 Dec;18(12):979-990. doi: 10.1016/j.hpb.2016.09.007. Epub 2016 Oct 27.
The incidence of liver disease is increasing in USA. Animal models had shown glutathione species in plasma reflects liver glutathione state and it could be a surrogate for the detection of hepatocellular carcinoma (HCC).
The present study aimed to translate methods to the human and to explore the role of glutathione/metabolic prints in the progression of liver dysfunction and in the detection of HCC. Treated plasma from healthy subjects (n = 20), patients with liver disease (ESLD, n = 99) and patients after transplantation (LTx, n = 7) were analyzed by GC- or LC/MS. Glutathione labeling profile was measured by isotopomer analyzes of HO enriched plasma. Principal Component Analyzes (PCA) were used to determined metabolic prints.
There was a significant difference in glutathione/metabolic profiles from patients with ESLD vs healthy subjects and patients after LTx. Similar significant differences were noted on patients with ESLD when stratified by the MELD score. PCA analyses showed myristic acid, citric acid, succinic acid, l-methionine, d-threitol, fumaric acid, pipecolic acid, isoleucine, hydroxy-butyrate and glycolic, steraric and hexanoic acids were discriminative metabolites for ESLD-HCC vs ESLD-HCC subject status.
Glutathione species and metabolic prints defined liver disease severity and may serve as surrogate for the detection of HCC in patients with established cirrhosis.
在美国，肝病的发病率正在上升。动物模型显示血浆中的谷胱甘肽种类反映了肝脏谷胱甘肽状态，并且它可能是检测肝细胞癌（HCC）的替代指标。
本研究旨在将方法应用于人类，并探索谷胱甘肽/代谢指纹在肝功能障碍进展和HCC检测中的作用。通过气相色谱或液相色谱/质谱分析健康受试者（n = 20）、肝病患者（终末期肝病，n = 99）和移植后患者（肝移植，n = 7）的处理后血浆。通过富含HO的血浆的同位素异构体分析测量谷胱甘肽标记谱。主成分分析（PCA）用于确定代谢指纹。
终末期肝病患者与健康受试者及肝移植后患者的谷胱甘肽/代谢谱存在显著差异。根据终末期肝病模型（MELD）评分分层时，终末期肝病患者也有类似的显著差异。主成分分析显示，肉豆蔻酸、柠檬酸、琥珀酸、L-甲硫氨酸、D-苏糖醇、富马酸、哌啶酸、异亮氨酸、羟基丁酸以及乙醇酸、硬脂酸和己酸是终末期肝病合并肝细胞癌与终末期肝病未合并肝细胞癌患者状态的鉴别性代谢物。
谷胱甘肽种类和代谢指纹可确定肝病严重程度，并可能作为已确诊肝硬化患者肝细胞癌检测的替代指标。
