了解结直肠癌（CRC）的代谢变化并探索潜在的诊断生物标志物对于阐明其发病机制和降低死亡率至关重要。癌细胞通常源自癌组织并且可以容易地获得和培养。目前仍缺乏对不同阶段CRC细胞的系统研究。此外，还需要验证我们之前在人血清中的发现。采用基于超高效液相色谱串联高分辨率质谱（UHPLC-HRMS）的代谢组学和脂质组学全面测量四种不同条件下结直肠癌细胞中的代谢物和脂质。来自正常对照 (NR) 和 CRC 受试者的阶段和血清样本。应用单变量和多变量统计分析来选择组间差异代谢物和脂质。通过受试者工作特征曲线（ROC）分析筛选细胞和血清中均存在的对CRC具有良好诊断效果的生物标志物。此外，使用代谢物标准对潜在的生物标志物进行了验证。A、B、C 和 D 期 CRC 细胞的代谢和脂质谱存在显着差异。甘油磷脂 (GPL)、脂肪酸 (FA) 和氨基酸 (AA) 代谢失调在CRC进展中发挥着至关重要的作用，特别是由磷脂酰胆碱（PC）主导的GPL代谢。总共发现了 CRC 细胞四个阶段共有的 46 种差异代谢物和 29 种差异脂质。与对照组相比，CRC 患者的 CRC 细胞和血清中的八种代谢物显示出相同的趋势。其中，棕榈酰肉碱和鞘氨醇可以作为潜在的生物标志物，其在血清和细胞中的曲线下面积（AUC）值超过0.80。他们的小组在区分不同阶段的 CRC 细胞与正常细胞方面表现出优异的性能 (AUC = 1.00)。 据我们所知，这是第一项尝试使用细胞模型验证 CRC 患者血清代谢研究结果的研究。 PC、FA、AA代谢紊乱与CRC的发生密切相关，其中PC是更为关键的因素。由棕榈酰肉碱和鞘氨醇组成的组合可以作为诊断 CRC 的潜在生物标志物，有助于预防。© 2024。作者。

Understanding the metabolic changes in colorectal cancer (CRC) and exploring potential diagnostic biomarkers is crucial for elucidating its pathogenesis and reducing mortality. Cancer cells are typically derived from cancer tissues and can be easily obtained and cultured. Systematic studies on CRC cells at different stages are still lacking. Additionally, there is a need to validate our previous findings from human serum.Ultrahigh-performance liquid chromatography tandem high-resolution mass spectrometry (UHPLC-HRMS)-based metabolomics and lipidomics were employed to comprehensively measure metabolites and lipids in CRC cells at four different stages and serum samples from normal control (NR) and CRC subjects. Univariate and multivariate statistical analyses were applied to select the differential metabolites and lipids between groups. Biomarkers with good diagnostic efficacy for CRC that existed in both cells and serum were screened by the receiver operating characteristic curve (ROC) analysis. Furthermore, potential biomarkers were validated using metabolite standards.Metabolite and lipid profiles differed significantly among CRC cells at stages A, B, C, and D. Dysregulation of glycerophospholipid (GPL), fatty acid (FA), and amino acid (AA) metabolism played a crucial role in the CRC progression, particularly GPL metabolism dominated by phosphatidylcholine (PC). A total of 46 differential metabolites and 29 differential lipids common to the four stages of CRC cells were discovered. Eight metabolites showed the same trends in CRC cells and serum from CRC patients compared to the control groups. Among them, palmitoylcarnitine and sphingosine could serve as potential biomarkers with the values of area under the curve (AUC) more than 0.80 in the serum and cells. Their panel exhibited excellent performance in discriminating CRC cells at different stages from normal cells (AUC = 1.00).To our knowledge, this is the first research to attempt to validate the results of metabolism studies of serum from CRC patients using cell models. The metabolic disorders of PC, FA, and AA were closely related to the tumorigenesis of CRC, with PC being the more critical factor. The panel composed of palmitoylcarnitine and sphingosine may act as a potential biomarker for the diagnosis of CRC, aiding in its prevention.© 2024. The Author(s).