Novel Metabolic Biomarker for Early Detection and Prognosis to the Patients with Gastric Cardia Adnocarcinoma

Background: Gastric cardia adenocarcinoma (GCA), which has been normalized as type II of adenocarcinoma at esophagogastric junction in western countries. In clinical, most of the GCA patients are lack of early alarming symptoms, more than 90% of GCA patients were diagnosed at advanced stage, resulted in a very poor prognosis, with less than 20% of 5-year survival. Obviously, early detection for GCA plays crucial role in decreasing the high mortality. Metabolomics allows for appraisal of small molecular mass compounds in a biofluid, which may provide a way for finding biomarkers for GCA. Methods: The serum metabolic features of 276 curatively resected GCA patients and 588 healthy control participates were collected from the database of State Key Laboratory of Esophageal Cancer Prevention & Treatment and Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital of Zhengzhou University to discover the metabolic dysregulation by using the ultraperformance liquid chromatography-mass spectrometry (UPLC-MS). Joint pathway analysis with metabolites identified, survival analysis and auxiliary diagnosis metabolites were discussed in present work. Results: A sum of 200 known differential metabolites were obtained with p＜0.05 and fold change FC≥1.25 or FC≤0.8 by comparison GCA and healthy control participates. 12 metabolites significant correlated with survival (p＜0.05) and 17 metabolites for potential auxiliary diagnosis(FC＞1.5 or FC＜0.67) for GCA. Dysregulated arginine biosynthesis was an important pathway of GCA. 9 differential metabolites of 12-ketolithocholic acid, 2-Hydroxybutanoic acid, Aldosterone, All-trans-13,14-dihydroretinol, Hododeoxycholic acid, L-histidine, Malonic acid, Prostaglandin E2 and Sphingosine were identified as potential metabolic markers for distinguishing the GCA and healthy control (AUC=0.976, sensitivity =0.913, specificity =0.027, optimal cut off value=0.470). Conclusions: This work was first identified 12 metabolites significant correlated with survival and 17 metabolites for potential auxiliary diagnosis for GCA. In addition, arginine biosynthesis pathway metabolism showed important roles in GCA. Results provide the understanding of the molecular difference between GCA and healthy control. The novel plasma biomarkers panel could clearly distinguish GCA patients from the healthy control group. This finding may form the basis for the development of a minimally invasive method for GCA detection.