Liver-intestine cadherin predicts microvascular invasion and poor prognosis of hepatitis B virus-positive hepatocellular carcinoma.
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.
Ding
Zhen-Bin
ZB
Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
Shi
Ying-Hong
YH
Zhou
Jian
J
Shi
Guo-Ming
GM
Ke
Ai-Wu
AW
Qiu
Shuang-Jian
SJ
Wang
Xiao-Ying
XY
Dai
Zhi
Z
Xu
Yang
Y
Fan
Jia
J
D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D045744:Cell Line, Tumor; D005260:Female; D006509:Hepatitis B / Q000150:complications*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D034741:RNA, Small Interfering / Q000494:pharmacology; D016019:Survival Analysis; D019043:Vascular Neoplasms / Q000556:secondary*
C490584:CDH17 protein, human; D015820:Cadherins; D034741:RNA, Small Interfering