Prognostic significance of PAK4 expression in gastric cancer

J Clin Pathol. 2016 Jul;69(7):580-5. doi: 10.1136/jclinpath-2015-203330. Epub 2015 Nov 27.

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.

Keywords: CANCER RESEARCH; GASTRIC CANCER; GASTRIC PATHOLOGY; IMMUNOHISTOCHEMISTRY.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Proliferation / genetics
  • Disease Progression
  • Female
  • Humans
  • Lymphatic Metastasis / genetics
  • Lymphatic Metastasis / pathology
  • Male
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / metabolism*
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology
  • Prognosis
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Survival Rate
  • p21-Activated Kinases / genetics
  • p21-Activated Kinases / metabolism*

Substances

  • Biomarkers, Tumor
  • PAK4 protein, human
  • p21-Activated Kinases