The Study On Serum Metabonomics In Esophageal Squamous Cell Carcinoma Based On ~1H-NMR Spectroscopy

Purpose: Esophageal cancer is a high incidence tumor which ranked ninth in the world’s highest incidence of malignant tumors and eighth in malignant tumor mortality. Esophageal cancer is also high incidence in China which ranked fourth in the death of the tumor. About 300,000 people die each year from esophageal cancer, which is a great threat to human health and survival. It is very important to find a new method to the diagnosis the esophageal cancer because there are many disadvantages in the traditional diagnosis. Metabolism is an emerging discipline which can evaluate diseases through the comprehensive assessment of the level of metabolic changes in the implementation. Through studying 1H-NMRS of the serum of esophageal cancer patients, we are trying to find serum metabolites which is closely related to esophageal cancer by multivariate statically analyzing. Also, the tumor metabolic mechanism was explored so as to provide reference for the diagnosis of patients with esophageal carcinoma。Method: The serum of the preliminary diagnosis esophageal cancer patients and health person in North Sichuan Medical College Affiliated Hospital were collected and analyzed by 1D 1H-NMRS, respectively. The multivariate statistic analysis such as principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA) were performed to analysis the serum 1H-NMRS data. The characteristic variable were identified in the PLS-DA analysis model and the corresponding specific characteristic metabolites’ chemical structures, change significantly and change trend(increase or decrease) were elucidated by comparative analysis with the characteristic variable value combined with literature and metabolic network database.Results:1. Direct comparison of the nuclear magnetic resonance spectroscopy(1H-NMRS) can not identify the subtle differences of metabolites between esophageal cancer patients and the volunteers.2. In the PCA analysis, PC1 and PC2 is 48.6% and 16.5 % respectively in the PCA model score figure but the discrimination is poor between the esophageal cancer group and the control group.3. PLS-DA model(2D and 3D) can well discriminate the esophageal cancer patients and the control group(R2 = 0.749, Q2 = 0.639; Accuracy = 0.98). We finally identified the 8 esophageal cancer related characteristic metabolites : the urea propionic acid, acetic acid, guanidine acetic acid, pyruvic acid, L-glutamine, azelaic acid, dimethyl sulfide, erythritol in esophageal cancer group. The metabolism of all the identified characteristic metabolites were decreased compared with the control group with the significant difference(VIP > 1, P < 0.01).Conclusion:1. The 1H-NMRS study of serum metabolites can clearly distinguish the esophageal cancer experimental group and the control group. In patients, the change of glucose metabolism, fat metabolism, and nucleic acid metabolism are significantly compared with the control group.2. The metabonomic study combined with metabolites pathway analysis may be helpful to understand the mechanism of esophageal cancer.