1. Decrease of Fibulin-3 in Hepatocellular Carcinoma Indicates Poor Prognosis.
- Author
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Luo, Rongzhen, Zhang, Meifang, Liu, Lili, Lu, Shixun, Zhang, Chris Zhiyi, and Yun, Jingping
- Subjects
FIBULINS ,LIVER cancer ,WERNER'S syndrome ,IMMUNOHISTOCHEMISTRY ,MESSENGER RNA ,BIOMARKERS ,GASTROENTEROLOGY ,PROGNOSIS - Abstract
Fibulin-3, originally identified in senescent and Werner syndrome fibroblasts, has been implicated in cell morphology, growth, adhesion and motility. Fibulin-3 exhibits both antitumor and oncogenic activities towards human cancers; however, the role of Fibulin-3 in hepatocellular carcinoma (HCC) remains elusive. In this study, we showed that both the mRNA and protein levels of Fibulin-3 were remarkably downregulated in HCC cell lines and fresh tissues. Immunohistochemical data revealed that Fibulin-3 was decreased in tumorous tissues in 67.1% (171/255) of cases compared to the corresponding adjacent nontumorous tissues. The results of statistical analysis indicated that low Fibulin-3 expression, defined by the receiver operating characteristic curve (ROC), was significantly associated with tumor differentiation (P = 0.008), clinical stage (P = 0.014) and serum AFP levels (P<0.01). Furthermore, Kaplan-Meier and multivariate analysis suggested that Fibulin-3 is an independent negative prognostic indicator for both overall (P<0.001) and recurrence-free (P = 0.036) survival. In addition, an in vitro study demonstrated that knockdown of Fibulin-3 by siRNA markedly increased cell viability and promoted cell invasion in HCC cells. Collectively, our data suggest that Fibulin-3 exhibits antitumor effects towards HCC and serves as a biomarker of unfavorable prognosis for this deadly disease. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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