UPLC-Q-TOF-MS-based unbiased serum metabolomics investigation of cholangiocarcinoma

作者：Xiaowei Wang, Xuefeng Xu, Jia Ran, Yuanhong Xu, Ping Hu · 发表于：Frontiers in Molecular Biosciences · 年份：2025 · DOI：10.3389/fmolb.2025.1549223 · 被引用次数：4 · 研究领域：Metabolomics and Mass Spectrometry Studies、Sphingolipid Metabolism and Signaling、Cholangiocarcinoma and Gallbladder Cancer Studies

Objective: Cholangiocarcinoma (CCA) is a highly aggressive malignancy, and early diagnosis remains challenging. Metabolic biomarkers are increasingly recognized as promising tools for the early detection of cancer. However, a comprehensive exploration of metabolic alterations in CCA, especially from a global metabolic perspective, has yet to be fully realized. To identify reliable metabolic markers for the early diagnosis of CCA and to explore its potential pathogenesis through an in-depth analysis of global metabolism. Methods: Serum samples from 30 CCA patients and 31 healthy individuals were analyzed using an unbiased UPLC-Q-TOF-MS based metabolomics approach. Principal component analysis (PCA) and orthogonal projections to latent structures discriminant analysis (OPLS-DA) were applied to identify potential biomarkers. High-resolution MS/MS and available standards were used to further confirm the identified metabolites. A systematic metabolic pathway analysis was conducted to interpret the biological roles of these biomarkers and explore their relevance to CCA progression. Results: A total of 25 marker metabolites were identified, including lysophosphatidylcholines (LysoPCs), phosphatidylcholines (PCs), organic acids, sphinganine, and ketoleucine. These metabolites effectively distinguished CCA patients from healthy controls, with an AUC of 0.995 for increased biomarkers and 0.992 for decreased biomarkers in positive mode. In negative mode, the AUC for increased and decrea...