title: Programmed cell death protein 1 expression is an independent prognostic factor in gastric cancer after curative resection.
abstract: BACKGROUND
  Programmed cell death protein 1 (PD-1) and its ligand PD-L1 downregulate T cell activation and are related to immune tolerance. The aim of this study was to clarify the significance of PD-1 and PD-L1 expression and to analyze the relationships among PD-1, PD-L1, and Foxp3 expression in gastric cancer.
  
  
  METHODS
  A total of 105 patients who underwent curative gastrectomy for stage II/III gastric cancer were included in this study. PD-1, PD-L1, and Foxp3 expression were examined by immunohistochemistry and related to prognostic factors by univariate and multivariate analyses.
  
  
  RESULTS
  PD-1 expression was correlated with both PD-L1 and Foxp3 expression. Disease-free survival (DFS) was significantly poorer in PD-1-positive patients than in PD-1-negative patients (3-year DFS, 36.1 % vs. 64.7 %, respectively; p < 0.05). Overall survival also tended to be poorer in PD-L1-positive patients than in PD-L1-negative patients. Univariate analysis identified sex, T factor, lymphatic invasion, and PD-1 positivity as significant predictors of poor DFS. Multivariate analysis confirmed male sex, lymphatic invasion, and positive PD-1 expression as independent prognostic indicators.
  
  
  CONCLUSIONS
  PD-1 expression is associated with a poor prognosis and is correlated with PD-L1 and Foxp3 expression in patients with gastric cancer.
authors.affiliation: Department of Surgery, Graduate School of Medical Sciences, University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Shohei
authors.initials: S
authors.lastname: Eto
authors.affiliation: Department of Surgery, Graduate School of Medical Sciences, University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan. yoshikawa.kozo@tokushima-u.ac.jp.
authors.forename: Kozo
authors.initials: K
authors.lastname: Yoshikawa
authors.affiliation: Department of Surgery, Graduate School of Medical Sciences, University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Nishi
authors.affiliation: Department of Surgery, Graduate School of Medical Sciences, University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Higashijima
authors.affiliation: Department of Surgery, Graduate School of Medical Sciences, University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Tokunaga
authors.affiliation: Department of Surgery, Graduate School of Medical Sciences, University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nakao
authors.affiliation: Department of Surgery, Graduate School of Medical Sciences, University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Hideya
authors.initials: H
authors.lastname: Kashihara
authors.affiliation: Department of Surgery, Graduate School of Medical Sciences, University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Takasu
authors.affiliation: Department of Surgery, Graduate School of Medical Sciences, University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Iwata
authors.affiliation: Department of Surgery, Graduate School of Medical Sciences, University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Shimada
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005743:Gastrectomy; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology / Q000601:surgery*
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: Gastric cancer; Programmed cell death 1; Programmed cell death ligand 1