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.
Highlights
Nectin-4 belongs to the nectin family that has diverse physiological and pathological functions in humans
Silencing of Nectin-4 inhibits proliferation of human pancreatic cancer cell we directly examined the function of Nectin-4 in pancreatic cancer cell using Small interfering RNA (siRNA) silencing
Accumulating evidence indicates that the nectins and nectin-like molecules (Necl) belonging to the nectin family have diverse physiological and pathological functions in humans [12,13,14]
Summary
Nectin-4 belongs to the nectin family that has diverse physiological and pathological functions in humans. Recent studies have suggested some roles for Nectin-4 in several human cancers. The nectins (Nectin-1, Nectin-2, Nectin-3, and Nectin-4) and nectin-like molecules (Necl) are families of Ca2 + -independent immunoglobulin-like cell adhesion molecules These members are important in the formation and maintenance of adherens junctions and tight junctions [12,13,14]. It was recently reported that Nectin-4 is overexpressed in several human cancers, including lung, ovarian, and breast cancer [17,18,19,20]. A few clinical studies have shown that there were significant inverse correlations between tumor Nectin-4 expression and the prognosis of the patients with lung and breast cancers [17,19]
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