RRLC-MS/MS-based metabonomics combined with in-depth analysis of metabolic correlation network: finding potential biomarkers for breast cancer

被引：206

作者：

Chen, Yanhua ^{[1
,2
]}

Zhang, Ruiping ^{[1
,2
]}

Song, Yongmei ^{[2
,3
,4
]}

He, Jiuming ^{[1
,2
]}

Sun, Jianghao ^{[1
,2
]}

Bai, Jinfa ^{[1
,2
]}

An, Zhuoling ^{[1
,2
]}

Dong, Lijia ^{[2
,3
,4
]}

Zhan, Qimin ^{[2
,3
,4
]}

Abliz, Zeper ^{[1
,2
]}

机构：

[1] Chinese Acad Med Sci, Inst Mat Med, Beijing 100050, Peoples R China

[2] Peking Union Med Coll, Beijing 100050, Peoples R China

[3] Chinese Acad Med Sci, Inst Canc, State Key Lab Mol Oncol, Beijing 100021, Peoples R China

[4] Chinese Acad Med Sci, Canc Hosp, Beijing 100021, Peoples R China

来源：

ANALYST | 2009年 / 134卷 / 10期

关键词：

ARYL-HYDROCARBON RECEPTOR; MASS-SPECTROMETRY; TRYPTOPHAN-METABOLISM; URINARY NUCLEOSIDES; IDENTIFICATION; DIAGNOSIS; MS; DISCOVERY; DISEASE; MARKER;

D O I：

10.1039/b907243h

中图分类号：

O65 [分析化学];

学科分类号：

070302 ; 081704 ;

摘要：

A metabonomics strategy based on rapid resolution liquid chromatography/tandem mass spectrometry (RRLC-MS/MS), multivariate statistics and metabolic correlation networks has been implemented to find biologically significant metabolite biomarkers in breast cancer. RRLC-MS/MS analysis by electrospray ionization (ESI) in both positive and negative ion modes was employed to investigate human urine samples. The resulting data matrices were analyzed using multivariate analysis. Application of orthogonal projections to latent structures discriminate analysis (OPLS-DA) allowed us to extract several discriminated metabolites reflecting metabolic characteristics between healthy volunteers and breast cancer patients. Correlation network analysis between these metabolites has been further applied to select more reliable biomarkers. Finally, high resolution MS and MS/MS analyses were performed for the identification of the metabolites of interest. We identified 12 metabolites as potential biomarkers including amino acids, organic acids, and nucleosides. They revealed elevated tryptophan and nucleoside metabolism as well as protein degradation in breast cancer patients. These studies demonstrate the advantages of integrating metabolic correlation networks with metabonomics for finding significant potential biomarkers: this strategy not only helps identify potential biomarkers, it also further confirms these biomarkers and can even provide biochemical insights into changes in breast cancer.

引用

页码：2003 / 2011

页数：9

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