Comprehensive Dipeptide Analysis Revealed Cancer-Specific Profile in the Liver of Patients with Hepatocellular Carcinoma and Hepatitis

As the physical properties and functionality of dipeptides differ from those of amino acids, they have attracted attention in metabolomics; however, their functions in vivo have not been clarified in detail. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, and its majo...

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Main Authors: Hitoshi Ozawa, Akiyoshi Hirayama, Futaba Shoji, Midori Maruyama, Kumi Suzuki, Hisami Yamanaka-Okumura, Hiroshi Tatano, Yuji Morine, Tomoyoshi Soga, Mitsuo Shimada, Masaru Tomita
Format: Article
Language:English
Published: MDPI AG 2020-11-01
Series:Metabolites
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Online Access:https://www.mdpi.com/2218-1989/10/11/442
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author Hitoshi Ozawa
Akiyoshi Hirayama
Futaba Shoji
Midori Maruyama
Kumi Suzuki
Hisami Yamanaka-Okumura
Hiroshi Tatano
Yuji Morine
Tomoyoshi Soga
Mitsuo Shimada
Masaru Tomita
author_facet Hitoshi Ozawa
Akiyoshi Hirayama
Futaba Shoji
Midori Maruyama
Kumi Suzuki
Hisami Yamanaka-Okumura
Hiroshi Tatano
Yuji Morine
Tomoyoshi Soga
Mitsuo Shimada
Masaru Tomita
author_sort Hitoshi Ozawa
collection DOAJ
description As the physical properties and functionality of dipeptides differ from those of amino acids, they have attracted attention in metabolomics; however, their functions in vivo have not been clarified in detail. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, and its major cause is chronic hepatitis. This study was conducted to explore tumor-specific dipeptide characteristics by performing comprehensive dipeptide analysis in the tumor and surrounding nontumor tissue of patients with HCC. Dipeptides were analyzed by liquid chromatography tandem mass spectrometry and capillary electrophoresis tandem mass spectrometry. Principal component analysis using 236 detected dipeptides showed differences in the dipeptide profiles between nontumor and tumor tissues; however, no clear difference was observed in etiological comparison. In addition, the N- and C-terminal amino acid compositions of the detected dipeptides significantly differed, suggesting the substrate specificity of enzyme proteins, such as peptidase. Furthermore, hepatitis-derived HCC may show a characteristic dipeptide profile even before tumor formation. These results provide insight into HCC pathogenesis and may help identify novel biomarkers for diagnosis.
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spelling doaj.art-cb01d272d53742a9a7159b7d51837d9a2023-11-20T19:26:06ZengMDPI AGMetabolites2218-19892020-11-01101144210.3390/metabo10110442Comprehensive Dipeptide Analysis Revealed Cancer-Specific Profile in the Liver of Patients with Hepatocellular Carcinoma and HepatitisHitoshi Ozawa0Akiyoshi Hirayama1Futaba Shoji2Midori Maruyama3Kumi Suzuki4Hisami Yamanaka-Okumura5Hiroshi Tatano6Yuji Morine7Tomoyoshi Soga8Mitsuo Shimada9Masaru Tomita10Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, JapanInstitute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, JapanInstitute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, JapanInstitute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, JapanInstitute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, JapanDepartment of Clinical Nutrition and Food Management, Graduate School of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, JapanDepartment of Clinical Nutrition and Food Management, Graduate School of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, JapanDepartment of Digestive and Pediatric Surgery, Graduate School of Medical Sciences, Tokushima University, Tokushima 770-8503, JapanInstitute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, JapanDepartment of Digestive and Pediatric Surgery, Graduate School of Medical Sciences, Tokushima University, Tokushima 770-8503, JapanInstitute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, JapanAs the physical properties and functionality of dipeptides differ from those of amino acids, they have attracted attention in metabolomics; however, their functions in vivo have not been clarified in detail. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, and its major cause is chronic hepatitis. This study was conducted to explore tumor-specific dipeptide characteristics by performing comprehensive dipeptide analysis in the tumor and surrounding nontumor tissue of patients with HCC. Dipeptides were analyzed by liquid chromatography tandem mass spectrometry and capillary electrophoresis tandem mass spectrometry. Principal component analysis using 236 detected dipeptides showed differences in the dipeptide profiles between nontumor and tumor tissues; however, no clear difference was observed in etiological comparison. In addition, the N- and C-terminal amino acid compositions of the detected dipeptides significantly differed, suggesting the substrate specificity of enzyme proteins, such as peptidase. Furthermore, hepatitis-derived HCC may show a characteristic dipeptide profile even before tumor formation. These results provide insight into HCC pathogenesis and may help identify novel biomarkers for diagnosis.https://www.mdpi.com/2218-1989/10/11/442dipeptidehepatocellular carcinomahepatitis B virushepatitis C virusliquid chromatography tandem mass spectrometrycapillary electrophoresis tandem mass spectrometry
spellingShingle Hitoshi Ozawa
Akiyoshi Hirayama
Futaba Shoji
Midori Maruyama
Kumi Suzuki
Hisami Yamanaka-Okumura
Hiroshi Tatano
Yuji Morine
Tomoyoshi Soga
Mitsuo Shimada
Masaru Tomita
Comprehensive Dipeptide Analysis Revealed Cancer-Specific Profile in the Liver of Patients with Hepatocellular Carcinoma and Hepatitis
Metabolites
dipeptide
hepatocellular carcinoma
hepatitis B virus
hepatitis C virus
liquid chromatography tandem mass spectrometry
capillary electrophoresis tandem mass spectrometry
title Comprehensive Dipeptide Analysis Revealed Cancer-Specific Profile in the Liver of Patients with Hepatocellular Carcinoma and Hepatitis
title_full Comprehensive Dipeptide Analysis Revealed Cancer-Specific Profile in the Liver of Patients with Hepatocellular Carcinoma and Hepatitis
title_fullStr Comprehensive Dipeptide Analysis Revealed Cancer-Specific Profile in the Liver of Patients with Hepatocellular Carcinoma and Hepatitis
title_full_unstemmed Comprehensive Dipeptide Analysis Revealed Cancer-Specific Profile in the Liver of Patients with Hepatocellular Carcinoma and Hepatitis
title_short Comprehensive Dipeptide Analysis Revealed Cancer-Specific Profile in the Liver of Patients with Hepatocellular Carcinoma and Hepatitis
title_sort comprehensive dipeptide analysis revealed cancer specific profile in the liver of patients with hepatocellular carcinoma and hepatitis
topic dipeptide
hepatocellular carcinoma
hepatitis B virus
hepatitis C virus
liquid chromatography tandem mass spectrometry
capillary electrophoresis tandem mass spectrometry
url https://www.mdpi.com/2218-1989/10/11/442
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