Expression of UPA and UPAR is associated with the clinical course of urinary bladder neoplasms.
The expression of urokinase plasminogen activator (uPA) and its receptor (uPAR) mRNA was determined in 194 subjects with newly detected bladder neoplasms, selected from a larger population-based series. An association was found between uPA and uPAR expression (n = 172; Spearman r(s) = 0.60, p < 0.001). Both uPA and uPAR mRNA levels were higher in muscle invasive (T2+) tumors than in noninvasive mucosal tumors (Ta) or those invading submucosa (T1). The relative hazard ratios (RHRs) for cancer-specific death associated with elevated expression (95% CI), adjusted for age and gender in a Cox proportional hazard model, were 1.8 (1.0-3.3) for uPA (upper quartile cut-line), 2.2 (1.3-4.0) for uPAR (median quartile cut-line) and 2.5 (1.3-4.9) for uPA + uPAR. An RHR for metastatic disease of 4.0 (1.6-9.9) was observed for uPAR. Restricting the analyses to T2+ tumors, the corresponding figures were: 2.1 (1.1-3.9) for uPA, 1.6 (0.8-3.3) for uPAR and 2.5 (1.1-5.6) for both. We conclude that expression of uPA and uPAR is associated with the clinical behaviour of bladder neoplasms, possibly providing means for refined staging of muscle invasive tumors and target proteins for novel therapies.
Cancer Center Karolinska, Karolinska Institute and Hospital, Stockholm, Sweden.
Maria
M
Seddighzadeh
Gunnar
G
Steineck
Per
P
Larsson
Hans
H
Wijkström
Ulf
U
Norming
Erik
E
Onelöv
Stig
S
Linder
D015870:Gene Expression; D006801:Humans; D009132:Muscles / Q000473:pathology; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000235:genetics*; D055293:Receptors, Urokinase Plasminogen Activator; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000628:therapy; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics*
C524898:PLAUR protein, human; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator