Comprehensive Dipeptide Analysis Revealed Cancer-Specific Profile in the Liver of Patients with Hepatocellular Carcinoma and Hepatitis
Hitoshi Ozawa,
Akiyoshi Hirayama,
Futaba Shoji,
Midori Maruyama,
Kumi Suzuki,
Hisami Yamanaka-Okumura,
Hiroshi Tatano,
Yuji Morine,
Tomoyoshi Soga,
Mitsuo Shimada,
Masaru Tomita
Affiliations
Hitoshi Ozawa
Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, Japan
Akiyoshi Hirayama
Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, Japan
Futaba Shoji
Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, Japan
Midori Maruyama
Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, Japan
Kumi Suzuki
Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, Japan
Hisami Yamanaka-Okumura
Department of Clinical Nutrition and Food Management, Graduate School of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, Japan
Hiroshi Tatano
Department of Clinical Nutrition and Food Management, Graduate School of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, Japan
Yuji Morine
Department of Digestive and Pediatric Surgery, Graduate School of Medical Sciences, Tokushima University, Tokushima 770-8503, Japan
Tomoyoshi Soga
Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, Japan
Mitsuo Shimada
Department of Digestive and Pediatric Surgery, Graduate School of Medical Sciences, Tokushima University, Tokushima 770-8503, Japan
Masaru Tomita
Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, Japan
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.
