Novel metabolic biomarker for early detection and diagnosis to the patients with gastric cardia adenocarcinoma.
Meng Xia Wei, Zheng Yang, Pan Pan Wang, Xue Ke Zhao, Xin Song, Rui Hua Xu, Jing Feng Hu, Kan Zhong, Ling Ling Lei, Wen Li Han, Miao Miao Yang, Fu You Zhou, Xue Na Han, Zong Min Fan, Jia Li, Ran Wang, Bei Li, Li Dong Wang
Author Information
Meng Xia Wei: State Key Laboratory of Esophageal Cancer Prevention & Treatment and Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan Province, PR China.
Zheng Yang: School of Life Science, Zhengzhou University, Zhengzhou, Henan Province, PR China.
Pan Pan Wang: State Key Laboratory of Esophageal Cancer Prevention & Treatment and Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan Province, PR China.
Xue Ke Zhao: State Key Laboratory of Esophageal Cancer Prevention & Treatment and Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan Province, PR China.
Xin Song: State Key Laboratory of Esophageal Cancer Prevention & Treatment and Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan Province, PR China.
Rui Hua Xu: State Key Laboratory of Esophageal Cancer Prevention & Treatment and Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan Province, PR China.
Jing Feng Hu: State Key Laboratory of Esophageal Cancer Prevention & Treatment and Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan Province, PR China.
Kan Zhong: State Key Laboratory of Esophageal Cancer Prevention & Treatment and Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan Province, PR China.
Ling Ling Lei: State Key Laboratory of Esophageal Cancer Prevention & Treatment and Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan Province, PR China.
Wen Li Han: State Key Laboratory of Esophageal Cancer Prevention & Treatment and Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan Province, PR China.
Miao Miao Yang: State Key Laboratory of Esophageal Cancer Prevention & Treatment and Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan Province, PR China.
Fu You Zhou: Department of Thoracic Surgery, Anyang Tumor Hospital, Anyang, Henan Province, PR China.
Xue Na Han: State Key Laboratory of Esophageal Cancer Prevention & Treatment and Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan Province, PR China.
Zong Min Fan: State Key Laboratory of Esophageal Cancer Prevention & Treatment and Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan Province, PR China.
Jia Li: Department of Language, Zhengzhou White Gown Translation Co., Ltd., Zhengzhou, PR China.
Ran Wang: State Key Laboratory of Esophageal Cancer Prevention & Treatment and Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan Province, PR China.
Bei Li: State Key Laboratory of Esophageal Cancer Prevention & Treatment and Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan Province, PR China.
Li Dong Wang: State Key Laboratory of Esophageal Cancer Prevention & Treatment and Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan Province, PR China. ORCID
BACKGROUND: Gastric cardia adenocarcinoma (GCA) is classified as Siewert type II adenocarcinoma at the esophagogastric junction in Western countries. The majority of GCA patients do not exhibit early warning symptoms, leading to over 90% of diagnoses at an advanced stage, resulting in a grim prognosis, with less than a 20% 5-year survival rate. METHOD: Metabolic features of 276 GCA and 588 healthy controls were characterized through a widely-targeted metabolomics by UPLC-MS/MS analysis. This study encompasses a joint pathway analysis utilizing identified metabolites, survival analysis in both early and advanced stages, as well as high and negative and low expression of HER2 immunohistochemistry staining. Machine learning techniques and Cox regression models were employed to construct a diagnostic panel. RESULTS: A total of 25 differential metabolites were consistently identified in both discovery and validation sets based on criteria of p���<���0.05, (VIP)���������1, and FC���������2 or FC���������0.5. Early-stage GCA patients exhibited a more favorable prognosis compared to those in advanced stages. HER2 overexpression was associated with a more positive outcome compared to the negative and low expression groups. Metabolite panel demonstrated a robust diagnostic performance with AUC of 0.869 in discovery set and 0.900 in validation set. CONCLUSIONS: A total of 25 common and stable differential metabolites may hold promise as liquid non-invasive indicators for GCA diagnosis. HER2 may function as a tumor suppressor gene in GCA, as its overexpression is associated with improved survival. The downregulation of bile acid metabolism in GCA may offer valuable theoretical insights and innovative approaches for precision-targeted treatments in GCA patients.
