title: Prognostic significance of PAK4 expression in gastric cancer.
abstract: OBJECTIVE
  p-21 activated kinase (PAK) 4, part of the six PAK families, plays an important role in growth factor signalling, cytoskeletal remodelling, gene transcription, cell proliferation and oncogenic transformation. However, the clinical significance of PAK4 in gastric cancer has yet to be fully elucidated. PAK4 expression was evaluated, and the correlations of PAK4 expression with clinicopathological features and outcomes in gastric cancer were examined.
  
  
  METHODS
  Gastric adenocarcinomas obtained from 217 patients who underwent gastrectomy were analysed. PAK4 expression was evaluated using immunohistochemical staining.
  
  
  RESULTS
  PAK4 overexpression was found in 95 (43.8%) of 217 tumours . High PAK4 expression was significantly correlated with clinicopathological variables related to tumour progression, including depth of invasion, metastatic lymph nodes, pathological stage, distant metastasis or recurrent disease. High PAK4 expression was significantly associated with poorer disease-specific survival (DSS) (p<0.001) and relapse-free survival (RFS) (p<0.001). On multivariable analysis, PAK4 was an independent prognostic factor for DSS (HR 2.5 (95% CI 1.4 to 4.7), p=0.003) and RFS (HR 2.8 (95% CI 1.4 to 5.6), p=0.004). Even in stage II and III disease, PAK4 was an independent prognostic factor for RFS (HR 2.2 (95% CI 1.1 to 4.5), p=0.029).
  
  
  CONCLUSIONS
  PAK4 may become a new prognostic factor in patients with gastric cancer.
authors.affiliation: Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Mikito
authors.initials: M
authors.lastname: Inokuchi
authors.affiliation: Department of Surgical Specialties, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Takagi
authors.affiliation: Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Otsuki
authors.affiliation: Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Fujimori
authors.affiliation: Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Yanaka
authors.affiliation: Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Higuchi
authors.affiliation: Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Aburatani
authors.affiliation: Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Chiharu
authors.initials: C
authors.lastname: Tomii
authors.affiliation: Department of Surgical Specialties, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Uetake
authors.affiliation: Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, Tokyo, Japan Center for Minimally Invasive Surgery, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Kojima
authors.affiliation: Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Tatsuyuki
authors.initials: T
authors.lastname: Kawano
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation / Q000235:genetics; D018450:Disease Progression; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D054462:p21-Activated Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C116367:PAK4 protein, human; D054462:p21-Activated Kinases
keywords: CANCER RESEARCH; GASTRIC CANCER; GASTRIC PATHOLOGY; IMMUNOHISTOCHEMISTRY