Nectin-4在肝细胞癌中的表达及临床意义
Expression and clinical significance of Nectin-4 in hepatocellular carcinoma.
作者信息
Ma Jie, Sheng ZhiYong, Lv Yang, Liu WenBin, Yao QiYang, Pan TingTing, Xu ZhiJun, Zhang ChuanHai, Xu GeLiang
机构信息
Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Affiliated Provincial Hospital of Anhui Medical University, Hefei, Anhui, People's Republic of China; Department of Hepatic Surgery, Affiliated Provincial Hospital of Anhui Medical University, Hefei, Anhui, People's Republic of China.
Medical Center, University of Science and Technology of China, Hefei, Anhui, People's Republic of China.
出版信息
Onco Targets Ther. 2016 Jan 6;9:183-90. doi: 10.2147/OTT.S96999. eCollection 2016.
OBJECTIVE
Nectin-4 is a member of the Nectin family of four Ca(+)-independent immunoglobulin-like cell adhesion molecules and implicated in cell adhesion, movement, proliferation, differentiation, polarization, and survival. The aberrant expression of Nectin-4 has been found in a variety of tumors; however, its expression in hepatocellular carcinoma (HCC) is still poorly understood. This study was to investigate the expression of Nectin-4 and its clinical significance in the patients with HCC.
METHODS
The expression of Nectin-4 was assessed at mRNA and protein levels by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting assays in 20 HCC specimens and adjacent non-tumor live tissues. Furthermore, the clinical significance of Nectin-4 in 87 cases of HCC was confirmed by immunohistochemistry.
RESULTS
The mRNA and protein levels of Nectin-4 were higher in HCC tumor tissues than in the matched non-tumor tissues. Nectin-4 was located in the cytoplasm of tumor cells and over-expressed in 67.82% (59/87) HCC tissues by immunohistochemical staining. Positive Nectin-4 expression was significantly correlated with tumor size (P=0.029), status of metastasis (P=0.023), vascular invasion (P=0.018) and tumor-node-metastasis stage (P=0.003). In addition, Kaplan-Meier survival analysis indicated that positive Nectin-4 expression was associated with worse recurrence-free survival (RFS) and overall survival (OS) (P=0.006 and P=0.005, respectively). In multivariate analysis, Nectin-4 was an independent prognostic factor for RFS and OS in the patients with HCC.
CONCLUSION
Nectin-4 is upregulated in HCC and may be a novel prognostic biomarker for the patients after surgical resection.
目的
Nectin-4是四种不依赖Ca(+)的免疫球蛋白样细胞粘附分子的Nectin家族成员之一，与细胞粘附、运动、增殖、分化、极化和存活有关。Nectin-4在多种肿瘤中存在异常表达；然而，其在肝细胞癌（HCC）中的表达仍知之甚少。本研究旨在探讨Nectin-4在HCC患者中的表达及其临床意义。
方法
采用定量逆转录聚合酶链反应（qRT-PCR）和蛋白质免疫印迹法检测20例HCC标本及癌旁非肿瘤肝组织中Nectin-4的mRNA和蛋白水平。此外，通过免疫组织化学法确定Nectin-4在87例HCC中的临床意义。
结果
HCC肿瘤组织中Nectin-4的mRNA和蛋白水平高于配对的非肿瘤组织。Nectin-4定位于肿瘤细胞的细胞质中，免疫组织化学染色显示67.82%（59/87）的HCC组织中Nectin-4过表达。Nectin-4阳性表达与肿瘤大小（P=0.029）、转移状态（P=0.023）、血管侵犯（P=0.018）及肿瘤-淋巴结-转移分期（P=0.003）显著相关。此外，Kaplan-Meier生存分析表明，Nectin-4阳性表达与无复发生存期（RFS）和总生存期（OS）较差相关（分别为P=0.006和P=0.005）。多因素分析显示，Nectin-4是HCC患者RFS和OS的独立预后因素。
结论
Nectin-4在HCC中上调，可能是手术切除后患者的一种新型预后生物标志物。
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