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. Therefore, our understanding of the mechanism underlying CCA recurrence is essential in order to prevent CCA recurrence and improve patient outcomes. We 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. At 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. Our 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.

中文翻译：

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全球代谢组学和脂质组学方法的整合揭示了早期胆管癌术后复发的分子机制和潜在的生物标志物

胆管癌（CCA）治疗具有挑战性，因为大多数患者在疾病晚期时被诊断出来，并且癌症复发是治疗后的主要问题，导致生存率低。因此，我们了解 CCA 复发的潜在机制对于预防 CCA 复发和改善患者预后至关重要。我们对 CCA 血清进行了基于 1H-NMR 和 UPLC-MS 的代谢组学。使用途径分析和潜在生物标志物鉴定进一步分析差异代谢物。在早期，参与能量代谢的代谢物，如丙酮酸代谢和 TCA 循环，被下调，而大多数脂质，包括 TGs、PC、PE 和 PAs，在复发患者中被上调。这种代谢特征已在癌症干细胞样细胞 (CSC) 代谢中进行了描述。此外，CSC 标志物 CD44v6 和 CD44v8-10 与 CD36（一种参与脂质摄取的蛋白质）以及无复发生存相关。我们还发现柠檬酸盐、肌氨酸、琥珀酸盐、肌酸、肌酐和丙酮酸以及 TG 对 CCA 复发具有良好的预测价值。我们的研究证明了 CCA 复发的可能分子机制，这些可能与 CSC 的存在有关。复发途径中涉及的代谢变化可用于确定预测 CCA 复发的生物标志物。我们的研究证明了 CCA 复发的可能分子机制，这些可能与 CSC 的存在有关。复发途径中涉及的代谢变化可用于确定预测 CCA 复发的生物标志物。我们的研究证明了 CCA 复发的可能分子机制，这些可能与 CSC 的存在有关。复发途径中涉及的代谢变化可用于确定预测 CCA 复发的生物标志物。