PURPOSE: The small GTP-binding protein Rho and its best-characterized downstream 
effector Rho-associated serine-threonine protein kinase, ROCK, participate in 
actin cytoskeleton organization, and are linked to pathogenesis and progression 
of several human tumors. We investigated the roles of Rho and ROCK in bladder 
cancer.
EXPERIMENTAL DESIGN: Using Western blotting, we quantitated Rho and ROCK protein 
expression in paired tumor and nontumor surgical samples from 107 consecutive 
Japanese patients with bladder cancer.
RESULTS: RhoA, RhoC, and ROCK were more abundant in tumors and metastatic lymph 
nodes than in nontumor bladder and uninvolved lymph nodes (P < 0.0001). Amounts 
of RhoA and RhoC protein, and ROCK protein expression correlated positively with 
one another (P < 0.0001). High RhoA, RhoC, and ROCK expression were related to 
poor tumor differentiation (P < 0.05, P < 0.01, and P < 0.01, respectively), 
muscle invasion (P < 0.001), and lymph node metastasis (P < 0.05). Kaplan-Meier 
plots linked high RhoA, RhoC, and ROCK protein expression to shortened 
disease-free and overall survival (P < 0.0001). By univariate analysis, high 
RhoA, RhoC, and ROCK protein expression predicted shortened disease-free and 
overall survival (P < 0.0001). By multivariate analysis, only RhoC was 
independently influenced in disease-free survival (P < 0.05), and RhoA and RhoC 
in overall survival (P < 0.001). In contrast, RhoB expression was inversely 
related to the grade and stage (P < 0.05), and its higher expression is 
associated with better overall survival (P < 0.05). In superficial tumors (Ta or 
T1; 63 patients), RhoA, RhoC, and ROCK were unrelated with recurrence-free 
survival. Overall survival in tumors invading muscle (T2 to T4; 44 patients) was 
significantly influenced by RhoA, RhoC, and ROCK in a Kaplan-Meier analysis (P < 
0.0001, P < 0.0001, and P < 0.01, respectively). Whereas RhoA, RhoC, and ROCK 
independently predicted shortened overall survival in patients with invasive 
tumor by univariate analysis (P < 0.0001, P < 0.0001, and P < 0.01, 
respectively), only RhoC did so by multivariate analysis (P < 0.05).
CONCLUSION: Rho/ROCK pathway apparently involved in occurrence and progression 
of bladder cancer may be valuable prognostic markers.