title: High RhoA expression at the tumor front in clinically localized prostate cancer and association with poor tumor differentiation.
abstract: Ras homolog gene family, member A (RhoA) has been reported as essential to the invasion process and aggressiveness of numerous cancers. However, there are only sparse data on the expression and activity of RhoA in clinically localised prostate cancer. In numerous cancers, tumour cells at the invasive front demonstrate more aggressive behaviour in comparison with the cells in the central regions. In the present study, the expression and activity of RhoA was evaluated in 34 paraffin-embedded and 20 frozen prostate tissue specimens obtained from 45 patients treated with radical prostatectomy for clinically localised cancer. The expression patterns of RhoA were assessed by immunohistochemical staining and western blotting. Additional comparisons were performed between the tumour centre, tumour front and distant peritumoural tissue. RhoA activity was assessed by G-LISA. Associations between RhoA expression and the clinical features and outcome of the patients were also analysed. The present study found an increasing gradient of expression from the centre to the periphery of index tumour foci. RhoA expression was significantly increased at the tumour front compared to the tumour centre, which was determined using immunohistochemistry (P=0.001). Increased RhoA expression was associated with poor tumour differentiation in the tumour front (P=0.044) and tumour centre (P=0.039). Subsequent to a median follow-up period of 52 months, the rate of prostate-specific antigen (PSA) relapse was increased in patients with higher RhoA expression at the tumour front when compared with patients with lower RhoA expression (62.5 vs. 35.0%), although the difference was not significant (P=0.09). There was no association between RhoA expression and the PSA level or pathological stage in the present study. In conclusion, RhoA expression was increased at the tumour front and was associated with poor tumour differentiation in the tumour front and tumour centre, indicating the potential role of RhoA in prostate cancer. RhoA expression may also act as a prognostic factor in prostate cancer. The present data provide a foundation for novel therapeutic approaches by targeting RhoA in prostate cancer.
authors.affiliation: Department of Urology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, P.R. China; Department of Functional Physiology, School of Medicine, Cochin Hospital, Paris Descartes University, Paris 75014, France.
authors.forename: Weihua
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Urology, Cochin Hospital, Paris Descartes University, Paris 75014, France.
authors.forename: Nicolas Barry
authors.initials: NB
authors.lastname: Delongchamps
authors.affiliation: Department of Urology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, P.R. China.
authors.forename: Kaili
authors.initials: K
authors.lastname: Mao
authors.affiliation: Department of Pathology, Cochin Hospital, Paris Descartes University, Paris 75014, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Beuvon
authors.affiliation: Department of Urology, Cochin Hospital, Paris Descartes University, Paris 75014, France.
authors.forename: Michaël
authors.initials: M
authors.lastname: Peyromaure
authors.affiliation: Clinical and Translational Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, P.R. China.
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Functional Physiology, School of Medicine, Cochin Hospital, Paris Descartes University, Paris 75014, France; Clinical and Translational Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, P.R. China.
authors.forename: Anh Tuan
authors.initials: AT
authors.lastname: Dinh-Xuan
keywords: Ras homolog gene family; invasive phenotype; member A; prostate cancer; tumour differentiation; tumour front