title: Expression of ribophorine II is a promising prognostic factor in human gastric adenocarcinoma.
abstract: The increased invasiveness of gastric adenocarcinoma is important for progression and metastasis. In recent molecular biological studies, ribophorine II (RPN2) induced epithelial-mesenchymal transition and metastatic activity. However, no studies have evaluated the relationship between RPN2 expression, ability of cancer to invade/metastasis, and patient prognosis in gastric adenocarcinoma. Therefore, we have examined these factors. Immunohistochemical staining was performed to detect RPN2 and p53 in the primary lesion and adjacent normal gastric mucosa of 242 gastric adenocarcinoma patients who underwent resection surgery. We conducted clinicopathologic examinations and analyzed patient prognoses with the Kaplan-Meier method. Further, multivariate analysis was conducted using a Cox hazard model. Also, we analyzed the ability of invasion under inhibited RPN2 expression in vitro. RPN2 expression was observed in 119 of 242 cases of gastric adenocarcinoma patients. RPN2 expression was associated with a higher incidence of depth of wall invasion, lymph node metastasis, lymphatic invasion, venous invasion, peritoneal dissemination, histopathological stage, and p53 expression. In stage II and III curative resection cases, where recurrence is the most serious problem, cases that expressed RPN2 had a significantly lower 5-year survival rate and higher recurrence rate compared to the cases with no RPN2 expression. In the multivariate analysis for prognosis, RPN2 expression was found to be an independent factor. Also, gastric adenocarcinoma cell, had mutant-type p53, reduced the ability of invasion by knockout of RPN2 expression in vitro. RPN2 expression correlates with gastric adenocarcinoma cell invasion and shows promise as a new prognostic factor in human gastric adenocarcinoma.
authors.affiliation: Department of Surgery 1, Faculty of Medicine, University of Fukui, Fukui 910-1193, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Fujimoto
authors.affiliation: Department of Surgery 1, Faculty of Medicine, University of Fukui, Fukui 910-1193, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Goi
authors.affiliation: Department of Surgery 1, Faculty of Medicine, University of Fukui, Fukui 910-1193, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Hirono
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005260:Female; D055785:Gene Knockdown Techniques; D006602:Hexosyltransferases / Q000032:analysis / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D009361:Neoplasm Invasiveness / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D046988:Proteasome Endopeptidase Complex / Q000032:analysis / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000401:mortality / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D006602:Hexosyltransferases; C517590:RPN2 protein, human; D046988:Proteasome Endopeptidase Complex