title: An improved diagnostic method for chronic hepatic disorder: analyses of metallothionein isoforms and trace metals in the liver of patients with hepatocellular carcinoma as determined by capillary zone electrophoresis and inductively coupled plasma-mass spectrometry.
abstract: It is desirable to diagnose hepatocellular carcinoma (HCC) in the early stages during its development since its treatment is usually difficult. We previously proposed a new diagnostic method that made use of the total metallothionein (MT), zinc (Zn), and copper (Cu) concentrations in the liver of the HCC patients. We recently found that MT-1 is involved in the metabolism or detoxification of toxic metals, such as cadmium; on the other hand, MT-2 is responsible for the homeostasis of essential metals such as copper, in experimental models such as Long Evans Cinnamon (LEC) rats. In order to device a better diagnostic method than the one we proposed previously, in this study, we newly propose an improved method that includes the discriminative determination data regarding the MT isomers, namely, MT-1 and MT-2, in the liver of patients with or without HCC as compared with the total MT level. The total MT and Zn concentrations in the HCC patients were confirmed to be significantly lower than those in patients without hepatic disorders (Ctrl). In contrast, Cu concentrations of the HCC patients were higher than those of the Ctrl patients. In addition, in the juxta-tumor portion with HCC, MT-1 concentrations were significantly higher than those of MT-2. In contrast, the MT-1 concentrations in the tumor portion were significantly lower than that in the juxta-tumor portion. In addition, MT-1/MT-2 ratio in the tumor portion was significantly lower than that of the juxta-tumor portion. By using parameters such as concentrations of Cu, Zn, total MT, and MT isomers, we performed the multivariate discriminative analysis (MDA). The results suggest that the concentrations of MT isomers change depending on the progress of the tumor, and information on MT isomers and trace elements is very useful in determining the stage of the chronic hepatic disorder.
authors.affiliation: Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Kawata
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Nakamura
authors.forename: Akihiro
authors.initials: A
authors.lastname: Nakayama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fukuda
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ebara
authors.forename: Takeaki
authors.initials: T
authors.lastname: Nagamine
authors.forename: Takeshi
authors.initials: T
authors.lastname: Minami
authors.forename: Hiromu
authors.initials: H
authors.lastname: Sakurai
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002908:Chronic Disease; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D019075:Electrophoresis, Capillary; D005260:Female; D006801:Humans; D007202:Indicators and Reagents; D007536:Isomerism; D008099:Liver / Q000737:chemistry* / Q000378:metabolism; D008107:Liver Diseases / Q000175:diagnosis* / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D008668:Metallothionein / Q000032:analysis* / Q000378:metabolism; D008670:Metals / Q000032:analysis* / Q000378:metabolism; D008875:Middle Aged; D015999:Multivariate Analysis; D051381:Rats; D020318:Rats, Long-Evans
chemical_list: D007202:Indicators and Reagents; D008670:Metals; D008668:Metallothionein