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.
Highlights
Hepatocellular carcinoma (HCC) is the fifth most prevalent malignancy diagnosed worldwide [1]
Etiology studies indicate that infection with a hepatitis virus (HBV or HCV) and the dysregulation of genes involved in cell proliferation are major risk factors for hepatocarcinogenesis [6,7]
We determined the expression of Fibulin-3 in HCC cell lines, using Quantitative Real-time PCR (qRT-PCR) and western blot
Summary
Hepatocellular carcinoma (HCC) is the fifth most prevalent malignancy diagnosed worldwide [1]. Its incidence has been increasing in economically developed regions, including Japan, Western Europe and the United States [2,3]. Surgical management and the clinical implementation of numerous therapeutic strategies, the mortality rate of HCC remains very high (up to 94%), making HCC the third most common cause of cancer-related death [1,4,5]. The accuracy and reproducibility of markers currently used in the clinic to predict prognosis after surgical resection are unsatisfactory [4].
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