Decrease of fibulin-3 in hepatocellular carcinoma indicates poor prognosis.
Decrease of fibulin-3 in hepatocellular carcinoma indicates poor prognosis.
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肝细胞癌中 Fibulin-3 的减少表明预后不良
DOI：
10.1371/journal.pone.0070511
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Yun J
中科院分区：
文献类型：
--
作者：
Luo R;Zhang M;Liu L;Lu S;Zhang CZ;Yun J
最初在衰老和Werner综合征成纤维细胞中鉴定的纤蛋白-3与细胞形态、生长、粘附和运动有关。Fibulin-3对人类癌症表现出抗肿瘤和致癌活性;然而，Fibulin-3在肝细胞癌（HCC）中的作用仍然难以捉摸。在这项研究中，我们发现Fibulin-3的mRNA和蛋白水平在肝癌细胞系和新鲜组织中均显著下调。免疫组化结果显示Fibulin-3在67.1%（171/255）的肿瘤组织中表达低于相应的癌旁组织。统计学分析结果表明，Fibulin-3低表达与肿瘤分化程度（P = 0.008）、临床分期（P = 0.014）和血清AFP水平（P<0.01）有关。 此外，Kaplan-Meier和多变量分析表明，Fibulin-3是总体（P<0.001）和无复发（P = 0.036）生存期的独立阴性预后指标。 此外，体外研究表明，通过siRNA敲低Fibulin-3显著增加HCC细胞中的细胞活力并促进细胞侵袭。总的来说，我们的数据表明，Fibulin-3对HCC表现出抗肿瘤作用，并作为这种致命疾病预后不良的生物标志物。
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.
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影响因子：
11.5
作者：
Kim, Yong-June;Yoon, Hyung-Yoon;Kim, Wun-Jae
通讯作者：
Kim, Wun-Jae
影响因子：
11.2
作者：
Albig, AR;Neil, JR;Schiemann, WP
通讯作者：
Schiemann, WP
DOI：
10.1056/nejmoa1115050
发表时间：
2012-10-11
期刊：
The New England journal of medicine
影响因子：
--
作者：
Pass HI;Levin SM;Harbut MR;Melamed J;Chiriboga L;Donington J;Huflejt M;Carbone M;Chia D;Goodglick L;Goodman GE;Thornquist MD;Liu G;de Perrot M;Tsao MS;Goparaju C
通讯作者：
Goparaju C
影响因子：
6.4
作者：
Sadr-Nabavi, Ariane;Ramser, Juliane;Meindl, Alfons
通讯作者：
Meindl, Alfons
血清 DKK1 作为诊断肝细胞癌的蛋白质生物标志物：一项大规模、多中心研究。
影响因子：
51.1
作者：
Shen, Qiujin;Fan, Jia;Qin, Wenxin
通讯作者：
Qin, Wenxin