Leukemia inhibitory factor receptor is a novel immunomarker in distinction of well-differentiated HCC from dysplastic nodules.

Leukemia inhibitory factor receptor is a novel immunomarker in distinction of well-differentiated HCC from dysplastic nodules.
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白血病抑制因子受体是区分分化良好的 HCC 和发育不良结节的新型免疫标志物

DOI:
10.18632/oncotarget.3136
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发表时间:
2015-03-30
期刊:
影响因子:
--
通讯作者:
Qin W
Qin W
中科院分区:
其他
文献类型:
--
作者:
Luo Q;Zhang Y;Wang N;Jin G;Jin H;Gu D;Tao X;Huo X;Ge T;Cong W;Wang C;Qin W

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鉴别诊断高分化肝细胞癌(WD-HCC)和高级别发育不良结节(hgdn)对病理学家来说是一个挑战。已经确定了几种免疫组织化学标记物来区分肝细胞癌(HCC)和hgdn。然而,单个标记物的敏感性或特异性仍然有限。在这项研究中,我们分析了白血病抑制因子受体(LIFR)和CD34在肝癌从发育不良结节到小肝癌发生过程中的动态变化。采用logistic回归模型研究LIFR和CD34联合诊断WD-HCC和hgdn的效能,并在独立验证队列中进行验证。随着肝癌从低级别发育不良结节(lgdn)到小肝癌的逐步进展,LIFR降低,CD34升高。LIFR和CD34联合检测WD-HCC的敏感性和特异性分别为93.5%和90.5%。此外,利用集落形成实验探讨了LIFR在肿瘤发生中的作用。沉默LIFR可显著促进肝癌细胞集落形成,而异位过表达LIFR则导致肝癌细胞集落形成能力受损。这些发现表明,在临床实践中,LIFR和CD34联合可作为从hgdn中鉴别WD-HCC的有效模型。
Differential diagnosis of well-differentiated hepatocellular carcinoma (WD-HCC) and high-grade dysplastic nodules (HGDNs) represents a challenge for pathologists. Several immunohistochemistry markers have been identified to distinguish hepatocellular carcinoma (HCC) from HGDNs. However, sensitivity or specificity of the individual marker is still limited. In this study, we analyzed dynamic alteration of leukemia inhibitory factor receptor (LIFR) and CD34 during hepatocarcinogenesis from dysplastic nodules to small HCC. The diagnostic performance of LIFR and CD34 combination in WD-HCC and HGDNs was investigated by logistic regression models and validated in an independent validation cohort. LIFR was decreased and CD34 was increased along with stepwise progression of hepatocarcinogenesis from low-grade dysplastic nodules (LGDNs) to small HCC. The sensitivity and specificity of the LIFR and CD34 combination for WD-HCC detection were 93.5% and 90.5%, respectively. In addition, colony formation assay was used to explore the role of LIFR in tumorigenesis. Silencing of LIFR could significantly promote colony formation of HCC cells, whereas ectopic overexpression of LIFR resulted in impaired ability of colony formation of HCC cells. These findings indicate that LIFR and CD34 combination may be used as an available differential diagnostic model for WD-HCC from HGDNs in clinical practice.
一组新颖的生物标志物,可区分小型分化良好的 HCC 与发育不良结节及结果值
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