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1H-NMR-based metabolomics reveals the biomarker panel and molecular mechanism of hepatocellular carcinoma progression

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Abstract

Hepatocellular carcinoma (HCC) is one of the most extensive and most deadly cancers in the world. Biomarkers for early diagnosis of HCC are still lacking, and noninvasive and effective biomarkers are urgently needed. Metabolomics is committed to studying the changes of metabolites under stimulation, and provides a new approach for discovery of potential biomarkers. In the current work, 1H nuclear magnetic resonance (NMR) metabolomics approach was utilized to explore the potential biomarkers in HCC progression, and the biomarker panel was evaluated by receiver operating characteristic (ROC) curve analyses. Our results revealed that a biomarker panel consisting of hippurate, creatinine, putrescine, choline, and taurine might be involved in HCC progression. Functional pathway analysis showed that taurine and hypotaurine metabolism is markedly involved in the occurrence and development of HCC. Furthermore, our results indicated that the TPA activity and the level and expression of PKM2 were gradually increased in HCC progression. This research provides a scientific basis for screening potential biomarkers of HCC.

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Abbreviations

HCC:

Hepatocellular carcinoma

NMR:

Nuclear magnetic resonance

ROC:

Receiver operating characteristic

AFP:

Alpha-fetoprotein

DEN:

Diethylnitrosamine

LC:

Liver cirrhosis

AKP:

Alkaline phosphatase

AST:

Aspartate aminotransferase

ALT:

Alanine aminotransferase

γ-GT:

Gamma-glutamyl transpeptidase

ELISA:

Enzyme-linked immunosorbent assay

TPA:

Taurine-pyruvate aminotransferase

SPF:

Specific pathogen-free

HE:

Hematoxylin and eosin

PCA:

Principal component analysis

PLS-DA:

Partial least-squares discriminant analysis

OPLS-DA:

Orthogonal partial least-squares discriminant analysis

FDR:

False discovery rate

AUC:

Area under the ROC curve

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Funding

This project was supported by the Base Program of Joint training graduate student of Shanxi Province (no. 2016JD05), Science and Technology Innovation Team of Shanxi Province (no. 201605D131045–18), and the Key laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, China (201705D111008–21).

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Authors and Affiliations

  1. Modern Research Center for Traditional Chinese Medicine, the Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan, China

    Ke-xin Wang, Guan-hua Du, Xue-mei Qin & Li Gao

  2. Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, Taiyuan, China

    Ke-xin Wang, Xue-mei Qin & Li Gao

  3. Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

    Guan-hua Du

Authors
  1. Ke-xin Wang
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  2. Guan-hua Du
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  3. Xue-mei Qin
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  4. Li Gao
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Contributions

X.-M. Qin and L. Gao provided the concept and designed the study. K.-X. Wang performed the experiments and drafted the manuscript. K-X. Wang and L. Gao participated in data analysis. X.-M. Qin, G.-H. Du and L. Gao provided oversight. L. Gao contributed to revising and proofreading the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Xue-mei Qin or Li Gao.

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Ethics approval

This study was approved in accordance with the ethical standards and approved by SXU Ethics Committee. All the recommendations in the National Institutes of Health Guidelines for Care and Use of Laboratory Animals were strictly followed in this study.

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The authors have no conflicts of interest, either real or potential, associated with this work.

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Wang, Kx., Du, Gh., Qin, Xm. et al. 1H-NMR-based metabolomics reveals the biomarker panel and molecular mechanism of hepatocellular carcinoma progression. Anal Bioanal Chem 414, 1525–1537 (2022). https://doi.org/10.1007/s00216-021-03768-9

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