Abstract
BackgroundCholangiocarcioma (CCA) treatment is challenging because most of the patients are diagnosed when the disease is advanced, and cancer recurrence is the main problem after treatment, leading to low survival rates. Therefore, our understanding of the mechanism underlying CCA recurrence is essential in order to prevent CCA recurrence and improve patient outcomes.MethodsWe performed 1H-NMR and UPLC-MS-based metabolomics on the CCA serum. The differential metabolites were further analyzed using pathway analysis and potential biomarker identification.ResultsAt an early stage, the metabolites involved in energy metabolisms, such as pyruvate metabolism, and the TCA cycle, are downregulated, while most lipids, including TGs, PCs, PEs, and PAs, are upregulated in recurrence patients. This metabolic feature has been described in cancer stem-like cell (CSC) metabolism. In addition, the CSC markers CD44v6 and CD44v8-10 are associated with CD36 (a protein involved in lipid uptake) as well as with recurrence-free survival. We also found that citrate, sarcosine, succinate, creatine, creatinine and pyruvate, and TGs have good predictive values for CCA recurrence.ConclusionOur study demonstrates the possible molecular mechanisms underlying CCA recurrence, and these may associate with the existence of CSCs. The metabolic change involved in the recurrence pathway might be used to determine biomarkers for predicting CCA recurrence.
Highlights
Cholangiocarcioma (CCA) treatment is challenging because most of the patients are diagnosed when the disease is advanced, and cancer recurrence is the main problem after treatment, leading to low survival rates
Patient characteristics and patient outcomes A total 102 CCA patients were enrolled in this study, and we firstly analyzed the association of patient characteristics including age, sex, tumor site, histology type, and tumor staging (according to the 7th edition of the American Joint Committee on Cancer (AJCC) Staging Manual) with clinical outcomes, including recurrencefree survival (RFS) and overall survival (OS)
Our results indicated that patient outcomes were mostly affected by the stage of cancer, including primary tumor (T stage) (RFS; p = 0.021, OS; p < 0.001), lymph node metastasis (N stage) (OS; p < 0.001), distant metastasis (M stage) (OS; p < 0.001), and TNM stage (RFS; p = 0.007, OS; p < 0.001) (Fig. S1 and S2)
Summary
Cholangiocarcioma (CCA) treatment is challenging because most of the patients are diagnosed when the disease is advanced, and cancer recurrence is the main problem after treatment, leading to low survival rates. Cholangiocarcinoma (CCA), known as bile duct cancer, is a malignant tumor that originates from the bile duct epithelium [1] It has the highest incidence in Northeast Thailand where there is a high incidence of Opisthorchis viverrini (OV) infection, the major risk factor of CCA development in this region [2]. We reported the association of CSCs and recurrence with the overexpression of putative cancer stem-like cell (CSC) markers. These have the potential to predict CCA recurrence [7]. The study of the mechanism underlying CCA recurrence is still essential for managing disease and improving patient outcomes
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