title: Prognostic impact of RING box protein-1 (RBX1) expression in gastric cancer.
abstract: BACKGROUND
  RING box protein-1 (RBX1) is an essential component of the E3 ubiquitin ligase Skp1/Cullin/RBX1/F-box protein complex. Although an altered expression of RBX1 has been reported in several human cancers, the role of RBX1 in gastric cancer remains unknown.
  
  
  METHODS
  We investigated the RBX1 expression in primary gastric cancer tissues from 145 patients by immunohistochemistry, and explored its clinical relevance and prognostic value. Furthermore, the effect of RBX1 expression on cancer cell proliferation was analyzed in vitro using a siRNA silencing technique.
  
  
  RESULTS
  The RBX1 expression was abundant in gastric cancer tissues. There was a significant difference in the expression level of RBX1 in terms of the tumor depth (P = 0.008), presence of distant metastasis (P = 0.016) and venous invasion (P = 0.005). The postoperative overall (P < 0.001) and relapse-free survival (P < 0.001) rates were significantly poorer in patients with RBX1-high tumors than in patients with RBX1-low tumors. There was a significant correlation of the RBX1 status with postoperative hematogenous recurrence (P = 0.013). Importantly, the RBX1 status was identified as an independent prognostic factor for gastric cancer (P = 0.002). Furthermore, RBX1 gene silencing significantly inhibited the proliferation of gastric cancer cells in vitro.
  
  
  CONCLUSIONS
  The RBX1 expression has a significant prognostic value in gastric cancer. RBX1 might play an important role in regulating the proliferation of gastric cancer cells and promoting the development of postoperative recurrence. Our data provide a rationale for developing a novel therapy targeting RBX1 for gastric cancer.
authors.affiliation: Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan, kmigita@naramed-u.ac.jp.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Migita
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Takayama
authors.forename: Sohei
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Kohei
authors.initials: K
authors.lastname: Wakatsuki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tanaka
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ito
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nishiwada
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Nakajima
mesh_terms: D000368:Aged; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011184:Postoperative Period; D011237:Predictive Value of Tests; D011379:Prognosis; D034741:RNA, Small Interfering; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery
chemical_list: D002352:Carrier Proteins; C479529:RBX1 protein, human; D034741:RNA, Small Interfering