Significant association of Rho/ROCK pathway with invasion and metastasis of bladder cancer

Takao Kamai1, Toshihiko Tsujii, Kyoko Arai

  • 1Department of Urology, Dokkyo University School of Medicine, Tochigi 321-0293, Japan. kamait@dokkyomed.ac.jp

Abstract

Insights

The Rho/ROCK pathway is involved in bladder cancer progression. High expression of RhoA, RhoC, and Rho-associated kinase (ROCK) correlates with poor prognosis, while RhoB indicates better survival, suggesting their potential as prognostic markers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The Rho GTP-binding protein and its effector Rho-associated kinase (ROCK) are implicated in the pathogenesis and progression of various human tumors.
  • These proteins play a crucial role in organizing the actin cytoskeleton, a process vital for cell structure and motility.

Purpose of the Study:

  • To investigate the specific roles of Rho and ROCK in the development and progression of bladder cancer.
  • To evaluate the potential of Rho and ROCK as prognostic markers in bladder cancer patients.

Main Methods:

  • Western blotting was employed to quantify the protein expression levels of Rho (RhoA, RhoB, RhoC) and ROCK.
  • Protein expression was analyzed in paired surgical samples of bladder tumors and adjacent non-tumor tissues from 107 Japanese patients.
  • Statistical analyses, including correlation, univariate, and multivariate analyses, were performed to assess the relationship between protein expression and clinical parameters.

Main Results:

  • RhoA, RhoC, and ROCK were significantly upregulated in bladder tumors and metastatic lymph nodes compared to non-tumor tissues (P < 0.0001).
  • Higher expression of RhoA, RhoC, and ROCK correlated with poor tumor differentiation, muscle invasion, and lymph node metastasis.
  • Elevated RhoA, RhoC, and ROCK levels were associated with significantly shortened disease-free and overall survival (P < 0.0001).
  • RhoB expression showed an inverse relationship with tumor grade and stage, and its higher expression was linked to better overall survival (P < 0.05).
  • In muscle-invasive bladder cancers, RhoA, RhoC, and ROCK independently predicted shortened overall survival, with RhoC being a significant independent predictor in multivariate analysis.

Conclusions:

  • The Rho/ROCK signaling pathway is demonstrably involved in the occurrence and progression of bladder cancer.
  • RhoA, RhoC, and ROCK protein expression levels serve as valuable prognostic markers for bladder cancer patients.
  • RhoB may represent a marker for a less aggressive form of bladder cancer.

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