Yu Lin, Lai Qinhuai, Feng Qian, Li Yuanmeng, Feng Jiafu, Xu Bei
Departmant of Clinical Laboratory, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China.
Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
Front Oncol. 2021 Mar 11;11:636917. doi: 10.3389/fonc.2021.636917. eCollection 2021.
Gastric cancer is a common tumor of the digestive system. Identification of potential molecules associated with gastric cancer progression and validation of potential biomarkers for gastric cancer diagnosis are very important. Thus, the aim of our study was to determine the serum metabolic characteristics of the serum of patients with chronic gastritis (CG) or gastric cancer (GC) and validate candidate biomarkers for disease diagnosis.
A total of 123 human serum samples from patients with CG or GC were collected for untargeted metabolomic analysis UHPLC-Q-TOF/MS to determine characteristics of the serum. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and heat map were used for multivariate analysis. In addition, commercial databases were used to identify the pathways of metabolites. Differential metabolites were identified based on a heat map with a -test threshold ( < 0.05), fold-change threshold (FC > 1.5 or FC < 2/3) and variable importance in the projection (VIP >1). Then, differential metabolites were analyzed by receiver operating characteristic (ROC) curve to determine candidate biomarkers. All samples were analyzed for fasting lipid profiles.
Analysis of serum metabolomic profiles indicated that most of the altered metabolic pathways in the three groups were associated with lipid metabolism ( < 0.05) and lipids and lipid-like molecules were the predominating metabolites within the top 100 differential metabolites ( < 0.05, FC > 1.5 or FC < 2/3, and VIP >1). Moreover, differential metabolites, including hexadecasphinganine, linoleamide, and N-Hydroxy arachidonoyl amine had high diagnostic performance according to PLS-DA. In addition, fasting lipid profile analysis showed the serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 (Apo-A1) were decreased concomitant to the progression of the progression of the disease compared with those in the control group ( < 0.05).
Thus, this study demonstrated that lipid metabolism may influence the development of CG to GC. Hexadecasphinganine, linoleamide, and N-Hydroxy arachidonoyl amine were selected as candidate diagnostic markers for CG and GC.
胃癌是消化系统常见肿瘤。鉴定与胃癌进展相关的潜在分子以及验证胃癌诊断的潜在生物标志物非常重要。因此，本研究的目的是确定慢性胃炎（CG）或胃癌（GC）患者血清的代谢特征，并验证疾病诊断的候选生物标志物。
收集了123例CG或GC患者的人血清样本，用于非靶向代谢组学分析（超高效液相色谱-四极杆飞行时间质谱法，UHPLC-Q-TOF/MS）以确定血清特征。主成分分析（PCA）、偏最小二乘判别分析（PLS-DA）和热图用于多变量分析。此外，使用商业数据库来识别代谢物的途径。基于具有t检验阈值（P<0.05）、倍数变化阈值（FC>1.5或FC<2/3）和投影中变量重要性（VIP>1）的热图来鉴定差异代谢物。然后，通过受试者工作特征（ROC）曲线分析差异代谢物以确定候选生物标志物。对所有样本进行空腹血脂谱分析。
血清代谢组学谱分析表明，三组中大多数改变的代谢途径与脂质代谢相关（P<0.05），并且脂质和类脂质分子是前100种差异代谢物中的主要代谢物（P<0.05，FC>1.5或FC<2/3，且VIP>1）。此外，根据PLS-DA，包括十六碳鞘氨醇、亚油酰胺和N-羟基花生四烯酰胺在内的差异代谢物具有较高的诊断性能。此外，空腹血脂谱分析显示，与对照组相比，随着疾病进展，总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）和载脂蛋白A1（Apo-A1）的血清水平降低（P<0.05）。
因此，本研究表明脂质代谢可能影响CG向GC的发展。十六碳鞘氨醇、亚油酰胺和N-羟基花生四烯酰胺被选为CG和GC的候选诊断标志物。
