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基于液相色谱-串联质谱法的胰腺导管腺癌淋巴结转移差异的血清代谢组学研究

Serum Metabonomics Study of Difference in Lymph Node Metastasis of Pancreatic Ductal Adenocarcinoma Based on LC-MS

  • 摘要:
    目的 探讨胰腺导管腺癌(PDAC)淋巴结转移的差异代谢物,为转移性胰腺癌的发病机制以及早诊早治提供新的思路。
    方法 收集PDAC患者血清标本40例,分为淋巴结转移组(18例)及未转移组(22例),另收集健康对照组血清标本31例。液相色谱-串联质谱法(LC-MS)分析PDAC患者与健康体检组、PDAC淋巴结转移组与未转移组差异代谢物以及代谢通路。
    结果 经主成分分析、偏最小二乘判别分析发现PDAC患者与健康体检组、淋巴结转移组与未转移组代谢轮廓差异有统计学意义。在PDAC患者与健康体检组之间筛选出76种差异代谢物和11条代谢通路,其中苯丙氨酸代谢、组氨酸代谢为影响最大的两条代谢通路;淋巴结转移组与未转移组筛选出4种差异代谢物,其中表达上调的有乙丙嗪、苯丙氨酸;表达下降的有四氢脱氧皮质酮、氧烯洛尔。
    结论 PDAC患者淋巴结转移组与未转移组代谢物发生显著改变,乙丙嗪、苯丙氨酸、四氢脱氧皮质酮、氧烯洛尔是PDAC患者淋巴结转移的潜在生物标志物。

     

    Abstract:
    Objective To investigate the differential metabolites of lymph node metastasis in pancreatic ductal carcinoma (PDAC) and provide new ideas for the pathogenesis, early diagnosis and treatment of metastatic pancreatic cancer.
    Methods Forty serum specimens of patients with pancreatic ductal carcinoma were collected and divided into lymph node metastasis group (18 cases) and non-metastasis group (22 cases). Thirty-one serum specimens were also collected from the healthy control group. Liquid chromatographytandem mass spectrometry was used to analyze the differential metabolites and metabolic pathways between patients with PDAC and healthy controls as well as between lymph node metastasis and non-metastasis groups.
    Results Principal component analysis and partial least squares-discriminant analysis revealed statistically significant differences in metabolites and metabolic pathways between patients with PDAC and the healthy controls and between lymph node metastasis and non-metastasis groups. The differences in profiles were also statistically significant. Seventy-six different metabolites and 11 metabolic pathways were screened between patients with PDAC and the healthy controls, among which phenylalanine metabolism and histidine metabolism were the two most influential metabolic pathways. Four different metabolites were screened between lymph node metastasis and non-metastasis groups, and the expression of ethopropazine and phenylalanine were upregulated but the expression of tetrahydrodeoxycorticosterone and oxprenolol were downregulated.
    Conclusion Metabolites are significantly altered in the lymph node metastasis group of patients with PDAC compared with the non-metastasis group. Ethopropazine, phenylalanine, tetrahydrodeoxy corticosterone, and oxprenolol are potential biomarkers of lymph node metastasis in patients with PDAC.

     

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