Decrease of fibulin-3 in hepatocellular carcinoma indicates poor prognosis.

[werner syndrome]

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 .

Diseases
Validation

Diseases presenting "hepatocellular carcinoma" symptom

cholangiocarcinoma

erythropoietic protoporphyria

esophageal adenocarcinoma

esophageal squamous cell carcinoma

primary hyperoxaluria type 1

severe combined immunodeficiency

werner syndrome

x-linked adrenoleukodystrophy

This symptom has already been validated