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Identifying Inhibitors of the HBx-DDB1 Interaction Using a Split Luciferase Assay System
Published on: December 21, 2019
Expression of DBC1 is associated with poor prognosis in hepatitis virus-related hepatocellular carcinoma
Sang Yun Ha1, Jeong Hoon Kim2, Jung Wook Yang1
1Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea.
Purpose:
Deleted in breast cancer 1 (DBC1) is a nuclear protein that was named by its deletion at a region 8p21 in some breast cancers and has been suggested as a poor prognostic indicator of various human cancers. However, the expression level of DBC1 protein and the prognostic role of DBC1 in hepatocellular carcinoma (HCC) have not been reported.
Methods:
We investigated the effect of DBC1 protein expression in 199 hepatitis virus-related HCC patients. Immunohistochemical expression of DBC1 were evaluated by tissue microarray.
Results:
High DBC1 immunoreactivity was observed in 177 (88.9%) of the 199HCC cases and was significantly associated with younger age (P=0.001), higher α-fetoprotein level (P=0.008), hepatitis B virus infection (P=0.001), and liver cirrhosis (P=0.003). High DBC1 expression showed an unfavorable effect on recurrence-free survival (RFS) (P=0.036) and tended to be an independent predictor of shorter RFS (P=0.064). High DBC1 expression did not show an unfavorable effect on overall survival (P=0.575). Five (45.5%) of 11 low grade dysplastic nodules (LGDNs), 8 (80%) of 10 high grade dysplastic nodules (HGDNs), and 10 (83.3%) of 12 early HCCs showed high DBC1 expression. The proportion of high DBC1 expression in LGDN, HGDN, early HCC, and HCC was significantly different, with a stepwise increase (P=0.0002).
Conclusion:
DBC1 protein could be a prognostic marker of shorter RFS in HCC patients after hepatectomy and human hepatocarcinogenesis was a multistep process accompanied by a stepwise increase in high DBC1 expression from LGDN, through HGDN, to HCC. Patients with high DBC1 expression can be considered candidates for adjuvant treatment after hepatectomy.
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