title: Nectin-4 expression contributes to tumor proliferation, angiogenesis and patient prognosis in human pancreatic cancer.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan. s-nishiwada@naramed-u.ac.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nishiwada
authors.affiliation: Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan. m-sho@naramed-u.ac.jp.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sho
authors.affiliation: Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan. hi22zd@gmail.com.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yasuda
authors.affiliation: Department of Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan. keijishi@naramed-u.ac.jp.
authors.forename: Keiji
authors.initials: K
authors.lastname: Shimada
authors.affiliation: Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan. yamato_16@me.com.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Yamato
authors.affiliation: Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan. akahorin@naramed-u.ac.jp.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Akahori
authors.affiliation: Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan. soysauce.1214@gmail.com.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Kinoshita
authors.affiliation: Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan. 34nm@naramed-u.ac.jp.
authors.forename: Minako
authors.initials: M
authors.lastname: Nagai
authors.affiliation: Department of Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan. nkonishi@naramed-u.ac.jp.
authors.forename: Noboru
authors.initials: N
authors.lastname: Konishi
authors.affiliation: Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan. nakayosh@naramed-u.ac.jp.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Nakajima
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015815:Cell Adhesion Molecules / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015870:Gene Expression; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D011379:Prognosis; D034622:RNA Interference; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D000075983:Nectins
chemical_list: D015815:Cell Adhesion Molecules; D019394:Ki-67 Antigen; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; C442228:NECTIN4 protein, human; D000075983:Nectins