title: DDX39 acts as a suppressor of invasion for bladder cancer.
abstract: The object of the present study was to identify markers for predicting urinary bladder cancer progression by comparative proteome analysis of bladder cancers and paired normal mucosas. We found that DDX39 was overexpressed in four of six bladder cancers examined compared with respective control tissues. Immunohistochemical analysis using 303 bladder cancer specimens revealed that DDX39 was inversely correlated to pT stage and histological grade progression. The incidence of DDX39(high) tumors (positive cells ≥50%) was 68.6%, 43.5%, 20.0%, and 5.3% in pTa, pT1, pTis, and ≥pT2 tumors, respectively, and 65.2%, 60.7%, and 19.6% in G1, G2, and G3 tumors, respectively. The incidence of DDX39(high) tumors was significantly lower in pT1 and ≥pT2 compared to pTa tumors, and also significantly lower in G3 compared to G1 and G2 tumors. Follow-up analysis (n = 105) revealed that DDX39(low) tumors (positive cells <50%) were associated with disease progression (hazard ratio 7.485; P = 0.0083). Furthermore, DDX39-knockdown bladder cancer cells increased their invasion ability compared to negative control cells. These results suggest that DDX39 is a suppressor of invasion and loss of its function predicts disease progression in bladder cancers.
authors.affiliation: Department of Pathology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Kato
authors.forename: Min
authors.initials: M
authors.lastname: Wei
authors.forename: Shotaro
authors.initials: S
authors.lastname: Yamano
authors.forename: Anna
authors.initials: A
authors.lastname: Kakehashi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tamada
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Nakatani
authors.forename: Hideki
authors.initials: H
authors.lastname: Wanibuchi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D020543:Proteome; D025521:Tumor Suppressor Proteins; C498428:DDX39A protein, human; D053487:DEAD-box RNA Helicases