Ubiquitin is a possible new predictive marker for the recurrence of human hepatocellular carcinoma.
OBJECTIVE
Ubiquitin (Ub)-dependent degradation of regulatory proteins controls many cellular processes such as cell cycle progression, morphogenesis and signal transduction. In this study, we evaluated the meaning of ubiquitination in chronic liver diseases, especially human hepatocellular carcinoma, with regard to recurrence.


METHODS
A total 74 of liver tissues (8 of chronic hepatitis [CH], 9 of liver cirrhosis [LC], 7 of dysplastic nodule low grade (DSL), or dysplastic nodule high grade (DSH)and 50 of hepatocellular carcinoma [HCC]) were analyzed for ubiquitination by immunohistochemistry. Cell proliferation was also analyzed using Ki-67 staining. As a comparative marker for progression of HCC, PIVKA-II (protein induced by vitamin K absence-II) was employed to examine the recurrence rate of HCC.


RESULTS
Ubiquitin (Ub) was positive in nuclei and cytoplasm of HCC in immunohistochemistry. The labeling index (L.I.) of ubiquitination was significantly higher with HCC than with other chronic liver diseases and tended to correlate with the lack of poorly-differentiated of HCC. The L.I. of Ki-67 staining was also correlated (P < 0.0001) with that of ubiquitination. The hepatocellular carcinoma (HCC) samples from potentially curatively operated patients having a ubiquitination L.I. of more than 20% suffered significantly higher recurrence of HCC than did patients with an L.I. of less than 20%. On the other hand, PIVA-II did not show such a difference.


CONCLUSIONS
Ubiquitin (Ub) may reflect the growth activity of neoplasms and will be a possible new predictive marker for the recurrence of human hepatocellular carcinoma after potentially curative operation.
Shirahashi
Hitoshi
H
First Department of Internal Medicine, Yamaguchi University School of Medicine, Ube, Japan.
Sakaida
Isao
I
Terai
Shuji
S
Hironaka
Koji
K
Kusano
Noriyoshi
N
Okita
Kiwamu
K
D015415:Biomarkers; D014408:Biomarkers, Tumor / Q000032:analysis*; D006528:Carcinoma, Hepatocellular / Q000737:chemistry / Q000175:diagnosis* / Q000601:surgery; D002455:Cell Division; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D008113:Liver Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000737:chemistry / Q000175:diagnosis*; D011498:Protein Precursors / Q000032:analysis; D011516:Prothrombin / Q000032:analysis; D025801:Ubiquitin / Q000032:analysis*
D015415:Biomarkers; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D011498:Protein Precursors; D025801:Ubiquitin; C008208:acarboxyprothrombin; D011516:Prothrombin