Nectin-4 expression contributes to tumor proliferation, angiogenesis and patient prognosis in human pancreatic cancer

作者：Nishiwada Satoshi; Sho Masayuki^*; Yasuda Satoshi; Shimada Keiji; Yamato Ichiro; Akahori Takahiro; Kinoshita Shoichi; Nagai Minako; Konishi Noboru; Nakajima Yoshiyuki

来源：Journal of Experimental & Clinical Cancer Research, 2015, 34(1): 30.

DOI：10.1186/s13046-015-0144-7

• Nectin-4
• Prognostic factor
• Pancreatic cancer
• Tumor angiogenesis

Background: Nectin-4 belongs to the nectin family that has diverse physiological and pathological functions in humans. Recent studies have also suggested some roles for Nectin-4 in several human cancers. However, the precise roles and clinical relevance of Nectin-4 in tumors are largely unknown.
Methods: Nectin-4 expression was investigated in 123 patients with pancreatic cancer by immunohistochemistry. Furthermore, we investigated the association of Nectin-4 in pancreatic cancer with tumor proliferation, angiogenesis and immunity by using immunohistochemistry and siRNA interference method.
Results: Patients with high Nectin-4 expression had poorer postoperative prognosis than those with low expression. Importantly, multivariate analysis indicated that Nectin-4 expression had a significant independent prognostic value in pancreatic cancer (HR = 1.721, 1.085-2.730; P = 0.021). Tumor Nectin-4 expression was significantly correlated with Ki67 expression. In addition, siRNA-mediated gene silencing of Nectin-4 significantly inhibited the cell proliferation in human pancreatic cancer cells, Capan-2 and BxPC-3. Furthermore, Nectin-4 expression was also positively correlated with VEGF expression and intratumoral microvessel density. However, there were no significant correlations of tumor Nectin-4 expression with tumor-infiltrating T cells.
Conclusion: Nectin-4 is a significant prognostic predictor, and may play a critical role in pancreatic cancer. Nectin-4 may be novel therapeutic target for pancreatic cancer.

• 出版日期2015-3-28