恶性淋巴瘤代谢组学研究内科学(血液)专业论文.docxVIP

恶性淋巴瘤代谢组学研究 摘要 目的：运用代谢组学技术从整体上考察淋巴瘤与正常人血清和尿液的代 谢物差异，筛选与淋巴瘤发病和疾病进展相关的代谢小分子标志物，进 一步分析相关代谢通路异常对淋巴瘤发病和疾病进展的影响。方法：本 研究运用超高压液相色谱-四级杆串联飞行时间质谱（UPLC Q-TOF MS） 技术分别分析了淋巴瘤患者血清 63 份，尿样 62 份；健康志愿者血清 80 份，尿样 30 份。进一步运用无监督的主成分分析（principle component analysis，PCA）和有监督的正交偏最小二乘法判别分析（orthogonal partial least square-discriminant analysis，OPLS-DA）对数据进行模式识别，分 析淋巴瘤患者和健康对照间的代谢差异，并进一步筛选差异物。结果： PCA 分析结果显示淋巴瘤患者与健康对照组的血清和尿液代谢谱有分离 趋势。OPLS-DA 模型能将 B 细胞淋巴瘤、T 细胞淋巴瘤和健康对照组的 三组样本分离，对三组样本建立两两组别的 OPLS-DA 模型，均能够得 到显著分离。对初步筛选的 1134 个代谢差异物分析提示淋巴瘤的代谢异 常与多不饱和脂肪酸、氨基酸及糖代谢显著相关。结论：淋巴瘤患者和 健康对照组间的血清和尿液代谢谱存在显著差异，即淋巴瘤患者存在代 谢异常，这种异常可能与多不饱和脂肪酸、氨基酸和糖代谢的异常相关。 关键词 淋巴瘤 代谢组学 分子标志物 代谢途径 Metabonomics study of malignant lymphoma ABSTRACT Objective: To investigate using metabonomics technology the metabolic differences between the serum and urine samples from lymphoma patients and healthy controls, to screen the small molecule biomarkers related to the lymphomagenesis and disease progression, and to further analyze the influence of the relevant metabolic pathway on lymphomagenesis and disease progression. Methods: We use the ultra high performance liquid chromatography - quadruple time of flight mass spectrometry (UPLC Q-TOF MS) technology to assess the serum of 63 lymphoma samples, 62 urine samples of 68 patients; 80 serum samples and 30 urine samples of healthy volunteers. We further use the unsupervised principal component analysis, PCA and supervised orthogonal partial least squares method discriminant analysis, OPLS-DA, the data pattern recognition, to analyze the metabolic differences between lymphoma patients and healthy controls. Results: The PCA results showed that serum and urine metabolic profiles of lymphoma patients are different from healthy controls. OPLS-DA model could well separate the B-cell lymphoma, T-cell lymphoma from healthy control group. Analysis of the 1134 initial screening of different metabilites showed that the metabolic abnormalities of lymphoma patients is significantly relevant to poly