Up regulation of Rho-associated coiled-coil containing kinase1 (ROCK1) is associated with genetic instability and poor prognosis in prostate cancer

Background and objectives: Overexpression of the cytoskeleton-modulating kinase ROCK1 has been associated with unfavorable outcome in many cancers, but its impact in prostate cancer is largely unknown. Results: A weak ROCK1 staining was found in >90% of normal, and cancerous prostate tissues, but was generally stronger in cancer cells as compared to adjacent normal glands. In cancer, ROCK1 staining was considered weak, moderate, and strong in 22%, 53%, and 18% of cases respectively. Higher ROCK1 expression levels were associated with tumor stage, and Gleason grade, positive nodal stage, positive surgical margin, accelerated cell proliferation and early PSA recurrence in multivariable analysis. ROCK1 up regulation was associated with androgen receptor (AR) expression, TMPRSS2:ERG fusion, genomic deletions of the PTEN tumor suppressor, as well as recurrent deletions at chromosomes 3p, 5q, 6q. Strong ROCK1 staining was found in 3% of AR-negative, but in 27% of strongly AR positive cancers, in 13% of ERG-negative but in 25% of ERG positive cancers, and in 12% of PTEN normal but in 26% of PTEN deleted cancers. Conclusions: This study identifies ROCK1 expression associated with prognosis in prostate cancer. Methods: We tested ROCK1 expression in 12 427 prostate cancer specimens and followed PSA recurrence after prostatectomy.

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