1. Nectin-4 expression contributes to tumor proliferation, angiogenesis and patient prognosis in human pancreatic cancer.
- Author
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Nishiwada S, Sho M, Yasuda S, Shimada K, Yamato I, Akahori T, Kinoshita S, Nagai M, Konishi N, and Nakajima Y
- Subjects
- Aged, Aged, 80 and over, Cell Line, Tumor, Cell Proliferation, Female, Gene Silencing, Humans, Immunohistochemistry, Ki-67 Antigen metabolism, Lymphocytes, Tumor-Infiltrating metabolism, Lymphocytes, Tumor-Infiltrating pathology, Male, Middle Aged, Neoplasm Grading, Neoplasm Metastasis, Neoplasm Staging, Pancreatic Neoplasms mortality, Pancreatic Neoplasms surgery, Prognosis, RNA Interference, RNA, Small Interfering, Vascular Endothelial Growth Factor A genetics, Vascular Endothelial Growth Factor A metabolism, Cell Adhesion Molecules genetics, Gene Expression, Neovascularization, Pathologic genetics, Pancreatic Neoplasms genetics, Pancreatic Neoplasms pathology
- Abstract
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.
- Published
- 2015
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