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Metabonomic classification and detection of small molecule biomarkers of malignant pleural effusions

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Abstract

To date, most research has been focused on the benign molecules in pleural effusions, and diagnosis of malignant ones still remains challenging. In the present study, targeting the small molecules as potential biomarkers to predict the malignancy of the effusions, the metabolic profiles of 81 clinical pleural effusions (41 malignant effusions from lung cancer and 40 benign ones) were investigated through a NMR-based metabonomic approach. In 1H NMR analysis, a total of ten small molecules in the effusions were simultaneously determined. Significantly higher mean values of valine, lactate, and alanine and markedly lower signal intensities of acetoacetate, trimethylamine-N-oxide, and α- and β-glucose were observed in malignant pleural effusions compared with those in benign ones. DFA modeling of NMR spectra subjected to a validation allowed the malignant effusions to be discriminated from benign ones in both training and validation groups. Currently, the conventional clinical analyses on chemical constituents in effusions could not provide a reliable prediction of malignancy of the effusions; the present results revealed that the small molecules might serve as useful biomarkers for diagnosis of the effusions, and the present NMR-based metabonomic approach provided a valuable potential to rapidly and sensitively predict the malignancy of the pleural effusions.

NMR based metabonomic analysis of pleural effusions and diagnostic results with discriminant function analysis

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Abbreviations

ATP:

Adenosine triphosphate

BPE:

Benign pleural effusion

CA:

Cancer antigen

CEA:

Carcinoembryonic antigen

DFA:

Discriminant function analysis

LDH:

Lactate dehydrogenase

MPE:

Malignant pleural effusion

NADH:

Nicotinamide adenine dinucleotide

NMR:

Nuclear magnetic resonance

OPLS-DA:

Orthogonal PLS-DA

PCA:

Principle component analysis

PLS-DA:

Partial least squares discriminant analysis

TMAO:

Trimethylamine-N-oxide

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Acknowledgments

This work was supported by the Project of Six Major Talents of Jiangsu Province (2009), National Natural Science Fund for Creative Research Groups of China (21121091), and the Fund of Affiliated Jiangsu Province Hospital of Traditional Chinese Medicine (Y11005).

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Authors and Affiliations

  1. Department of Respiratory Medicine, Affiliated Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing University of Traditional Chinese Medicine, Nanjing, 210029, China

    Xian-Mei Zhou & Yang Zhao

  2. State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210093, China

    Cui-Cui He, Yu-Mei Liu, Dan Zhao, Yun Du & Jian-Xin Li

  3. Innov Pharma, Suite 1004, 10 Xinghou Road, Nanjing High-Tech Zone, Nanjing, 210061, China

    Wei-Yi Zheng

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  1. Xian-Mei Zhou
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Zhou, XM., He, CC., Liu, YM. et al. Metabonomic classification and detection of small molecule biomarkers of malignant pleural effusions. Anal Bioanal Chem 404, 3123–3133 (2012). https://doi.org/10.1007/s00216-012-6432-6

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  • DOI: https://doi.org/10.1007/s00216-012-6432-6

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