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利用傅立叶变换离子回旋共振质谱技术探测肺癌的性别特异性脂质代谢物和诊断生物标志物。

Probing gender-specific lipid metabolites and diagnostic biomarkers for lung cancer using Fourier transform ion cyclotron resonance mass spectrometry.

机构信息

Department of Biophysics and Structural Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, PR China.

出版信息

Clin Chim Acta. 2012 Dec 24;414:135-41. doi: 10.1016/j.cca.2012.08.010. Epub 2012 Aug 18.

Abstract

BACKGROUND

There are no effective clinical biomarkers for early and specific detection of lung cancer (LC). The changes in the levels of some serum metabolites of LC patients are associated with patient gender and LC stages.

METHODS

Serum metabolites of the LC patients (n=58) and healthy controls (n=495) were performed using direct-infusion positive ion electrospray ionization-Fourier transform ion cyclotron resonance mass spectrometry in combination with univariate and partial least squares discriminant analyses (PLS-DA).

RESULTS

Univariate analysis indicated that 141 of the 212 serum metabolites were significantly changed in the LC patients compared with healthy controls. PLS-DA model, based on the 141 metabolites, demonstrated the differential metabolite distribution in single-sex LC patients compared with the corresponding healthy controls, and also in LC females compared with LC males. Several lipids comprising fatty acid derivations, sphingomyelin (SM) and lysophosphatidylcholine (LPC) were associated with the LC progression. Classification using oleamide, long chain acyl carnitines, LPC(18:1), LPC(20:4), LPC(20:3), LPC(22:6), and SM(16:0/1) as a biomarker panel resulted in remarkable separation between the LC patients and healthy controls with sensitivity and specificity of 100% and 91%, respectively.

CONCLUSION

The serum metabolites found in this study may play essential roles in gender-specific LC detection and early diagnosis of cancer.

摘要

背景

目前尚无有效的临床生物标志物用于早期和特异性检测肺癌(LC)。LC 患者血清代谢物水平的变化与患者性别和 LC 分期有关。

方法

采用直接进样正离子电喷雾电离傅里叶变换离子回旋共振质谱联用技术,结合单变量和偏最小二乘判别分析(PLS-DA)对 LC 患者(n=58)和健康对照者(n=495)的血清代谢物进行检测。

结果

与健康对照组相比,单变量分析显示 LC 患者的 212 种血清代谢物中有 141 种明显改变。基于这 141 种代谢物的 PLS-DA 模型显示,单性别 LC 患者与相应的健康对照组之间,以及 LC 女性与 LC 男性之间,差异代谢物的分布存在差异。几种包含脂肪酸衍生、神经鞘磷脂(SM)和溶血磷脂酰胆碱(LPC)的脂质与 LC 进展有关。使用油酸酰胺、长链酰基肉碱、LPC(18:1)、LPC(20:4)、LPC(20:3)、LPC(22:6)和 SM(16:0/1)作为生物标志物组合进行分类,结果表明 LC 患者与健康对照组之间的显著分离,其灵敏度和特异性分别为 100%和 91%。

结论

本研究发现的血清代谢物可能在性别特异性 LC 检测和癌症的早期诊断中发挥重要作用。

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