Research Papers:

Essential amino acids as diagnostic biomarkers of hepatocellular carcinoma based on metabolic analysis

Yuji Morine _, Tohru Utsunomiya, Hisami Yamanaka-Okumura, Yu Saito, Shinichiro Yamada, Tetsuya Ikemoto, Satoru Imura, Shohei Kinoshita, Akiyoshi Hirayama, Yasuhito Tanaka and Mitsuo Shimada

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Oncotarget. 2022; 13:1286-1298. https://doi.org/10.18632/oncotarget.28306

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Yuji Morine1, Tohru Utsunomiya1, Hisami Yamanaka-Okumura2, Yu Saito1, Shinichiro Yamada1, Tetsuya Ikemoto1, Satoru Imura1, Shohei Kinoshita3,4, Akiyoshi Hirayama3,4, Yasuhito Tanaka5 and Mitsuo Shimada1

1 Department of Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, Japan

2 Department of Clinical Nutrition and Food Management, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, Japan

3 Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, Japan

4 Systems Biology Program, Graduate School of Media and Governance, Keio University, Fujisawa, Kanagawa 252-0882, Japan

5 Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan

Correspondence to:

Yuji Morine, email: ymorine@tokushima-u.ac.jp

Keywords: metabolomics; essential amino acid; hepatocellular carcinoma; diagnostic biomarker

Received: October 03, 2022     Accepted: October 20, 2022     Published: November 22, 2022

Copyright: © 2022 Morine et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Metabolomics, defined as the comprehensive identification of all small metabolites in a biological sample, has the power to shed light on phenotypic changes associated with various diseases, including cancer. To discover potential metabolomic biomarkers of hepatocellular carcinoma (HCC), we investigated the metabolomes of tumor and non-tumor tissue in 20 patients with primary HCC using capillary electrophoresis–time-of-flight mass spectrometry. We also analyzed blood samples taken immediately before and 14 days after hepatectomy to identify associated changes in the serum metabolome. Marked changes were detected in the different quantity of 61 metabolites that could discriminate between HCC tumor and paired non-tumor tissue and additionally between HCC primary tumors and colorectal liver metastases. Among the 30 metabolites significantly upregulated in HCC tumors compared with non-tumor tissues, 10 were amino acids, and 7 were essential amino acids (leucine, valine, tryptophan, isoleucine, methionine, lysine, and phenylalanine). Similarly, the serum metabolomes of HCC patients before hepatectomy revealed a significant increase in 16 metabolites, including leucine, valine, and tryptophan. Our results reveal striking differences in the metabolomes of HCC tumor tissue compared with non-tumor tissue, and identify the essential amino acids leucine, valine, and tryptophan as potential metabolic biomarkers for HCC.

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