Expression and clinical significance of Nectin-4 in hepatocellular carcinoma

Abstract

Jie Ma,1,2,* ZhiYong Sheng,3,* Yang Lv,4,* WenBin Liu,1,2 QiYang Yao,1 TingTing Pan,1 ZhiJun Xu,1 ChuanHai Zhang,1,2 GeLiang Xu1,2 1Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, 2Department of Hepatic Surgery, Affiliated Provincial Hospital of Anhui Medical University, Hefei, Anhui, 3Medical Center, University of Science and Technology of China; 4Department of Plastic Surgery, The Second Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China *These authors contributed equally to this work 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. Keywords: Nectin-4, hepatocellular carcinoma, prognostic marker, RT-PCR, Western blot, immunohistochemistry 

Keywords

• Nectin-4
• Hepatocellular carcinoma
• Prognostic marker
• RT-PCR
• western blot
• immunohistochemistry