基于UPLC/MS技术的乳腺癌血清代谢组学研究

Serum metabonomics study on breast cancer with UPLC/MS

目的:探索乳腺癌患者与健康人血清代谢组学差异,为乳腺癌的鉴定与诊断寻找血清潜在生物标志物,推测乳腺癌的发生机理。方法:利用超高压液相色谱质谱(UPLC/MS)技术建立了乳腺癌血清代谢指纹图谱。分别采用主成分分析(PCA)、偏最小二乘法-判别分析(PLS-DA)和正交校正的偏最小二乘法-判别分析(OPLS-DA)分析病例组和正常对照组之间的代谢差异。结果:通过变量重要性投影,结合质谱同位素分析和数据库检索筛选鉴定出了9个潜在生物标志物,涉及核苷代谢、磷脂代谢、氨基酸代谢、脂肪酸代谢及皮质甾体激素代谢。结论:乳腺癌患者与健康对照人群在血清代谢水平上具有明显差异,差异代谢物的发现有助于为发现乳腺癌诊断的潜在标志物提供依据,推测哪些代谢通路参与了乳腺癌的发生发展,为乳腺癌发病机理研究与个体化治疗提供依据。

Objective：To investigate the difference of serum metabonome between breast cancer patients and healthy women using metabonomics approach,and to discover serum potential biomarkers for identification,diagnosis and exploring pathogenesis of breast cancer.Methods： The metabolic fingerprint of breast cancer serum was established based on UPLC/MS.The data were preprocessed with the software MarkerLynx,and analyzed with principle component analysis（PCA）,partial least squares discriminant analysis（PLS-DA） and orthogonal signal correction partial least squares discrimination analysis（OPLS-DA）.Results： Nine potential biomarkers were screened out according to the VIP（variable importance in projection） value and identified with i-fit and database.These potential biomarkers relate to several metabolic pathway including nucleotide metabolism,phospholipids metabolism,amino acid metabolism,fatty acid metabolism and cortical hormone metabolism.Conclusion： The distinct differences existed between breast cancer patients and healthy women on the serum metabolic level,and the potential biomarkers relative metabolic pathway may involve in the development of breast cancer.It therefore can contribute not only to the diagnosis of breast cancer but also to the pathogenesis of breast cancer,the study can contribute to the pathogenesis research about breast cancer.