Abstract
PurposeGastric 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.Experimental DesignA total of 123 human serum samples from patients with CG or GC were collected for untargeted metabolomic analysis via 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 t-test threshold (p < 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.ResultsAnalysis of serum metabolomic profiles indicated that most of the altered metabolic pathways in the three groups were associated with lipid metabolism (p < 0.05) and lipids and lipid-like molecules were the predominating metabolites within the top 100 differential metabolites (p < 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 (p < 0.05).ConclusionsThus, 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.
Highlights
Gastric cancer (GC) is a common digestive system tumor worldwide with a five-year survival rate ranging from 30 to 65% [1]
To avoid overfitting effect of partial least squares-discriminant analysis (PLS-DA) models, 200 random permutation tests were performed; the results indicated the absence of overfitting with R2X0 (0.33–0.38), Q2X0 (−0.36 to −0.43), R2Y (0.82–0.95), and Q2Y (0.74–0.94), demonstrating the differences in metabolic profiles between the control, chronic gastritis (CG), and GC groups (Figure 2)
The results indicated that linoleamide and N-Hydroxy arachidonoyl amine can be used as candidate biomarkers for CG, and hexadecasphinganine and linoleamide can be used as candidate biomarkers for GC
Summary
Gastric cancer (GC) is a common digestive system tumor worldwide with a five-year survival rate ranging from 30 to 65% [1]. The development of GC is a complex process involving environmental factors and molecular changes at the cellular level [2]. Gastric carcinoma involves mixed cell types with variable degrees of differentiation, and the majority of serum biomarkers have low sensitivity and low positive predictive value, such as CEA, CA199 and CA72-4 [6,7,8].
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