Liver-intestine cadherin predicts microvascular invasion and poor prognosis of hepatitis B virus-positive hepatocellular carcinoma.

Abstract

BACKGROUND:

Liver-intestine cadherin (LI-cadherin; CDH-17) is a new member of the cadherin superfamily with distinct structural and functional features. The study was designed to investigate the role of LI-cadherin in tumor invasion and prognosis of human hepatitis B virus (HBV)-positive hepatocellular carcinoma (HCC).

METHODS:

LI-cadherin expression in HBV-positive hepatocellular carcinoma cell lines with low- and high-invasive potentials was evaluated by Western-blot, immunofluorescence, and real-time polymerase chain reaction (PCR) analyses. The role of LI-cadherin in tumor invasion was also evaluated in vitro by a small-interfering ribonucleic acid (siRNA)-mediated approach. The prognostic significance of LI-cadherin was validated in a cohort of HBV-positive HCC patients by immunohistochemistry and Western-blot.

RESULTS:

Significant high levels of LI-cadherin mRNA and protein were found in the high-invasive HCCLM3 as compared with those in low-invasive PLC/PRF/5 and Hep3B cell line. Cell migration, adhesion to extracellular matrix, and matrigel invasion were significantly reduced after LI-cadherin knockdown in HCCLM3 cells. Immunohistochemical analysis of 255 HBV-positive HCC cases showed that overexpression of LI-cadherin was well correlated with microvascular invasion, which was confirmed by Western-blot in 32 tumor tissues, and its overexpression was strongly associated with shorter overall survival as well as higher incidence of tumor recurrence.

CONCLUSIONS:

LI-cadherin is predictive of microvascular invasion and poor prognosis of HBV-positive HCC, and would be a potential useful intervention target for HCC.

• Authors: Zhen-Bin Ding, Ying-Hong Shi, Jian Zhou, Guo-Ming Shi, Ai-Wu Ke, Shuang-Jian Qiu, Xiao-Ying Wang, Zhi Dai, Yang Xu, Jia Fan
• Journal: Cancer (Cancer) Vol. 115 Issue 20 Pg. 4753-65 (Oct 15 2009) ISSN: 0008-543X [Print] United States
• PMID: 19626651 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Validation Study)
• Copyright: Copyright (c) 2009 American Cancer Society.

Chemical References

• CDH17 protein, human
• Cadherins
• RNA, Small Interfering

Topics

• Cadherins (genetics, metabolism)
• Carcinoma, Hepatocellular (metabolism, pathology, virology)
• Cell Line, Tumor
• Female
• Hepatitis B (complications)
• Humans
• Liver Neoplasms (metabolism, pathology, virology)
• Male
• Microcirculation
• Middle Aged
• Neoplasm Invasiveness
• Prognosis
• RNA, Small Interfering (pharmacology)
• Survival Analysis
• Vascular Neoplasms (secondary)