Low expression of BARX2 in human primary hepatocellular carcinoma correlates with metastasis and predicts poor prognosis.
OBJECTIVE
The homeobox gene Barx2 was recently identified as a regulator of ovarian and breast cancer; however, the expression level of BARX2 and its significance in hepatocellular carcinoma (HCC) remain unknown.


METHODS
Protein and mRNA expression levels of Barx2 were examined using Western blotting and real-time PCR respectively, in paired HCC tissue and matched adjacent non-cancerous tissue from 12 patients. The expression levels of epithelial-mesenchymal transition (EMT) markers were also detected in relation to BARX2 expression. Lastly, immunohistochemistry for BARX2 was also performed on a tissue microarray containing 231 HCC tissue samples.


RESULTS
We observed that BARX2 expression was lower in HCC tissues compared to matching adjacent non-cancerous tissue. The low expression level of BARX2 was significantly correlated with metrics of tumor size, tumor differentiation, clinical stage, metastasis and relapse. Furthermore, the patients with low BARX2 expression had adverse survival outcomes. Importantly, multivariate Cox regression analysis revealed that low BARX2 expression was an independent marker for lower overall survival (P = 0.007). Moreover, a significant negative relationship was observed between the expression of BARX2 and markers of EMT.


CONCLUSIONS
These findings provide evidence that the low expression level of BARX2 in HCC is significantly correlated with tumor metastasis, and that BARX2 may be an independent prognostic biomarker for patients with HCC.
Department of Gastroenterology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou.
Yi
Y
Zhang
Jia-Xing
JX
Zhang
Lin-Lin
LL
Huang
Long-Jun
LJ
He
Yi-Ji
YJ
Liao
Ying-Rong
YR
Lai
Hai-Xia
HX
Deng
Xiao-Peng
XP
Tian
Hsiang Fu
HF
Kung
Dan
D
Xie
Sen-Lin
SL
Zhu
BARX2; epithelial-mesenchymal transition; hepatocellular carcinoma; metastasis; prognosis