乙肝相关性肝癌手术前后血清代谢轮廓分析及特征代谢物筛选

摘要

Objectives To investigate the characteristics of changes in serum metabolic profile before and after resection of carcinoma tissues to establish a disease distinguishing model,to analyze the changing trend of characteristic metabolites,and to determine the molecular mechanism and potential clinical value of characteristic metabolic markers for HBV-related liver cancer.Methods Ultraperformance liquid chromatography-mass spectrometry (UPLC-MS) was used to analyze the serum metabolites of 15 patients with hepatocellular carcinoma (HCC) before and after partial hepatectomy and on 25 healthy volunteers.The pattern recognition method and nonparametric test analyzes were used to analyze the data and to identify the specific metabolites and their changes after resection of carcinoma tissues.Results We established the principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) disease distinguishing model for HCC patients before and after operation as against the healthy volunteers.To distinguish between the liver cancer group and the normal control group,27 characteristic metabolites were selected from the patients before and after resection of carcinoma tissues.Eight moved towards the normal control after resection of carcinoma tissues.This indicated that liver carcinoma was an important impacting factor for these metabolites.Finally,7 metabolites were identified,and these metabolites had high diagnostic value as shown on ROC curves.Conclusions Through serum metabolic profiling of patients before and after resection of carcinoma tissues,a high correlation between metabolism and hepatocellular carcinoma was found.Researches on endogenous metabolites and pathways in liver diseases will provide a better understanding of the molecular mechanisms and provide further directions for clinical diagnosis and treatment.%目的 研究乙肝相关性肝癌患者手术前后血清代谢轮廓的变化,建立疾病区分模型并寻找特征代谢物,探讨其分子机制及特征代谢物的潜在临床价值.方法 应用超高效液相色谱与质谱联用(UPLC-MS)代谢组学分析平台对15例肝细胞癌(HCC)患者手术前后血清和25例健康志愿者血清样本进行分析,采用基于模式识别的多元统计学分析方法对实验数据进行处理并对差异性代谢物的变化趋势进行分析.结果 成功构建了HCC患者手术前后与健康对照组血清代谢轮廓的主成分分析模型(PCA)及正交偏最小二乘判别分析模型(OPLS-DA).从模型中筛选出27个在肝癌切除前后血清中存在显著差异的特征代谢离子.其中8个特征离子随着肝癌的切除其血清中的含量趋向正常,说明癌组织是影响这些特征代谢物变化的重要因素.对其中7个特征代谢离子进行了物质鉴定,ROC曲线表明这7种代谢物均具有较高的肝癌诊断价值.结论 通过对肝细胞癌患者手术前后血清代谢轮廓分析,找到了与肝癌高度相关的代谢信息.从内源性代谢物及代谢途径层面对肝癌疾病进行研究,有助于了解该疾病的分子机制,并对临床诊治提供新的方向.