Nectin-4 expression contributes to tumor proliferation,angiogenesis and patient prognosis in human pancreatic cancer |
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Authors: | Satoshi Nishiwada Masayuki Sho Satoshi Yasuda Keiji Shimada Ichiro Yamato Takahiro Akahori Shoichi Kinoshita Minako Nagai Noboru Konishi Yoshiyuki Nakajima |
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Institution: | .Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522 Japan ;.Department of Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522 Japan |
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Abstract: | BackgroundNectin-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.MethodsNectin-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.ResultsPatients 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.ConclusionNectin-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. |
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Keywords: | Nectin-4 Prognostic factor Pancreatic cancer Tumor angiogenesis |
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