Novel metabolic biomarker for early detection and diagnosis to the patients with gastric cardia adenocarcinoma

作者：Meng Xia Wei, Zheng Yang, Pan Pan Wang, Xue Zhao, Xin Song, Rui‐Hua Xu, Jing Feng Hu, Kan Zhong, Ling Ling Lei, Wen Li Han, Miao Yang, Fu You Zhou, Xue Han, Zong Min Fan, Jia Li, Ran Wang, Bei Li, Lidong Wang · 发表于：Cancer Medicine · 年份：2024 · DOI：10.1002/cam4.7015 · 被引用次数：7 · 研究领域：Gastric Cancer Management and Outcomes、Metabolomics and Mass Spectrometry Studies、Gut microbiota and health

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...