CD24 is a novel predictor for poor prognosis of hepatocellular carcinoma after surgery.
OBJECTIVE
To investigate the role of CD24 in tumor invasion and prognostic significance in hepatocellular carcinoma (HCC).


METHODS
CD24 expression was measured in stepwise metastatic HCC cell lines, tumor, peritumoral tissues, and normal liver tissues by quantitative real-time PCR and Western blot. The role of CD24 in HCC was investigated by CD24 depletion using small interfering RNA. Tumor tissue microarrays of 314 HCC patients who underwent resection between 1997 and 2000 were used to detect expression of CD24, beta-catenin, and proliferating cell nuclear antigen. Prognostic significance was assessed using Kaplan-Meier survival estimates and log-rank tests.


RESULTS
CD24 was overexpressed in the highly metastatic HCC cell line and in tumor tissues of patients with recurrent HCC. Depletion of CD24 caused a notable decrease in cell proliferation, migration, and invasiveness in vitro. Univariate and multivariate analyses revealed that CD24 was a significant predictor for overall survival and relapse-free survival. CD24 expression was correlated with poor prognosis independent of alpha-fetoprotein, tumor-node-metastasis stage, and Edmondson stage. High CD24 expression was significantly associated with cytoplasmic and nuclear accumulation of beta-catenin (P = 0.023), high tumor proliferative status (P = 0.018), and diffused intrahepatic recurrence and distant metastasis (P = 0.026). Adjuvant transcatheter arterial chemoembolization after surgery reduced the rate of early recurrence (<or=1 year) in CD24(+) HCC patients (P = 0.024) but had no significant effect in CD24(-) patients (P = 0.284).


CONCLUSIONS
Overexpression of CD24 in HCC was associated with high invasiveness and metastatic potential, high tumor proliferation status, and activation of the Wnt/beta-catenin pathway. CD24 may be a novel predictor for poor prognosis of HCC patients after surgery.
Yang
Xin-Rong
XR
Liver Cancer Institute, Zhong Shan Hospital and Shanghai Medical School, Fudan University, Key Laboratory for Carcinogenesis & Cancer Invasion, Chinese Ministry of Education, Shanghai, People's Republic of China.
Xu
Yang
Y
Yu
Bin
B
Zhou
Jian
J
Li
Jia-Chu
JC
Qiu
Shuang-Jian
SJ
Shi
Ying-Hong
YH
Wang
Xiao-Ying
XY
Dai
Zhi
Z
Shi
Guo-Ming
GM
Wu
Bin
B
Wu
Li-Ming
LM
Yang
Guo-Huan
GH
Zhang
Bo-Heng
BH
Qin
Wen-Xin
WX
Fan
Jia
J
D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D051927:CD24 Antigen / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D020868:Gene Silencing / Q000502:physiology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D015999:Multivariate Analysis; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D046888:Tissue Array Analysis; D000509:alpha-Fetoproteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
D014408:Biomarkers, Tumor; D051927:CD24 Antigen; D018809:Proliferating Cell Nuclear Antigen; D034741:RNA, Small Interfering; D000509:alpha-Fetoproteins; D051176:beta Catenin