The study of roles of Rho family GTPase in progression and metastasis of renal cell cancer

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We analyzed the mRNA levels of RhoA, RhoB, RhoC and ROCK gene in the surgical specimens of RCC tissues from 78 consecutive Japanese patients and in the corresponding non-tumor tissue originating from the same patient using polymerase chain reaction after reverse transcription (RT-PCR). We compared their expression levels in tumor tissues with those in non-tumor tissues and evaluated the relationship between their expression levels in tumors and clinicopathological features.The mRNA levels of RhoC and ROCK were increased in tumor tissues, compared with those in non-tumor tissues of the resected testis (P<0.0001, P<0.0001, respectively). There was no difference between the expression levels of mRNAs for RhoA. Although RhoB mRNA levels were higher in tumor tissues than those in non-tumor tissues (P<0.05), its expression was not associated with tumor grade, stage and prognosis. The increase of the RhoC and ROCK mRNA levels was related to the tumor grade (P<0.05, P<0.05, respectively) and s … More tage (P<0.0001, P<0.0001, respectively). There was a positive relationship between expression levels of mRNAs of RhoC and ROCK in tumor tissues (P<0.0001). Kaplan-Meier plots of survival rate in patients with low versus high mRNA levels of RhoC and ROCK showed that high mRNA levels of RhoC and ROCK were associated with overall survival (P<0.0001, P<0.0001, respectively). Multivariate analysis showed that mRNA levels of RhoC and ROCK were independent prognostic factors in overall survival.In renal pelvis and ureter cancer, the higher expression of RhoA and ROCK proteins were associated poorly differentiated grade, higher stage, and unfavorable prognosis 1).In bladder cancer, although the higher protein levels of RhoA, RhoC, and ROCK were related to poorly differentiated grade, higher stage, and unfavorable prognosis, the lower RhoB levels were shown in advanced tumors 2).In testicular germ cell tumor, the higher expressions of RhoA, ROCK, Rac1 and Cdc42 were associated with advanced stage of the disease 3). Less