title: Clinical significance of RacGAP1 expression at the invasive front of gastric cancer.
abstract: BACKGROUND
  Rac GTPase activating protein 1 (RacGAP1) plays a regulatory role in cell growth, transformation and metastasis. The aim of this study was to clarify the association between RacGAP1 expression and clinical outcome in patients with gastric cancer.
  
  
  METHODS
  A total of 232 gastric cancer patients in our institute who underwent surgery without preoperative treatments were enrolled in this study. We investigated RacGAP1 expression using immunohistochemistry (IHC) and evaluated IHC scores calculated by the percentage of positive cells and intensity and its expression at the invasive front. RACGAP1 expression was also assessed.
  
  
  RESULTS
  RacGAP1 expression was observed in the nuclei of gastric cancer cells. Evaluation by IHC score showed no significant correlations with clinicopathological variables except for histological differentiation. In transcriptional analyses, RACGAP1 expression was elevated in diffuse type gastric cancer than intestinal type without a significant difference. We observed significant correlations of RacGAP1 protein expression at the invasive front with older age, tumor size, lymph node metastasis, lymphatic invasion, vascular invasion and advanced stage. Patients with RacGAP1 protein expression at the invasive front had significantly poorer prognosis than those without it (P < 0.0001). In multivariate analysis, lymph node metastasis, distant metastasis and positive RacGAP1 expression at the invasive front were independent prognostic factors (lymph node metastasis: P = 0.0106; distant metastasis: P = 0.0012; RacGAP1: P = 0.0011).
  
  
  CONCLUSIONS
  RacGAP1 expression at the invasive front in gastric cancer was significantly correlated with factors reflecting tumor progression and poor prognosis. Our data suggest that RacGAP1 might play important roles in the progression of gastric cancer.
authors.affiliation: Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan, saigusa@clin.medic.mie-u.ac.jp.
authors.forename: Susumu
authors.initials: S
authors.lastname: Saigusa
authors.forename: Koji
authors.initials: K
authors.lastname: Tanaka
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Mohri
authors.forename: Masaki
authors.initials: M
authors.lastname: Ohi
authors.forename: Tadanobu
authors.initials: T
authors.lastname: Shimura
authors.forename: Takahito
authors.initials: T
authors.lastname: Kitajima
authors.forename: Satoru
authors.initials: S
authors.lastname: Kondo
authors.forename: Yoshinaga
authors.initials: Y
authors.lastname: Okugawa
authors.forename: Yuji
authors.initials: Y
authors.lastname: Toiyama
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Inoue
authors.forename: Masato
authors.initials: M
authors.lastname: Kusunoki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D005260:Female; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D020690:GTPase-Activating Proteins; C115995:mgcRacGAP; D020764:cdc42 GTP-Binding Protein