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Prognostic significance of PAK4 expression in gastric cancer
  1. Kenta Kobayashi1,
  2. Mikito Inokuchi1,
  3. Yoko Takagi2,
  4. Sho Otsuki1,
  5. Yoshitaka Fujimori1,
  6. Yuya Sato1,
  7. Yoshimitsu Yanaka1,
  8. Kyoko Higuchi1,
  9. Tomoki Aburatani1,
  10. Chiharu Tomii1,
  11. Hiroyuki Uetake2,
  12. Kazuyuki Kojima1,3,
  13. Tatsuyuki Kawano1
  1. 1Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, Tokyo, Japan
  2. 2Department of Surgical Specialties, Tokyo Medical and Dental University, Tokyo, Japan
  3. 3Center for Minimally Invasive Surgery, Tokyo Medical and Dental University, Tokyo, Japan
  1. Correspondence to Dr Mikito Inokuchi, Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan; m-inokuchi.srg2{at}tmd.ac.jp

Abstract

Aims 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.

  • GASTRIC CANCER
  • IMMUNOHISTOCHEMISTRY
  • GASTRIC PATHOLOGY
  • CANCER RESEARCH

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