January 23, 2007

Gene expression points to prostate cancer outcomes

The level of expression of various genes in prostate cancer potentially offers diagnostic information, and may even point to therapeutic outcomes, German study findings indicate.

Although clinico-pathological factors such as Gleason score and pT-stage are recognised diagnostic and prognostic factors, they often do not accurately predict the clinical outcome of individual cases, argue S Joos, from the German Cancer Research Center in Heidelberg, and colleagues.

Aiming to identify novel prostate cancer biomarkers, the team conducted an exhaustive gene search of seven genomic-profiling studies of 161 prostate tumours, along with four expression profiling studies of 61 tumours. The average age of the patients was 67 years. Six genes from the list of candidate genes that resulted from the search were selected for protein-expression analysis.

Using antibodies applicable to paraffinised tissue, the team examined the protein-expression of fatty acid synthase, MYC, beta-adrenergic receptor kinase 1 (BARK1, GRK2), the catalytic subunits of protein phosphatases PP1-alpha (PPP1CA) and PP2A (PPP2CB), and metastasis suppressor NM23-H1. Immunohistochemistry on a tissue microarray was used to analyze these candidates in 651 cores of prostate cancer samples, along with 175 samples of prostatic hyperplasia (BPH).

The results, published in the British Journal of Cancer, show that PP1-alpha expression was strongly correlated with Gleason score on univariate analysis. On both univariate and multivariate analysis, MYC immunostaining was negatively correlated with pT-stage and Gleason score. In addition, high Gleason scores were associated with a complete loss of the BARK1 protein.

"In conclusion, we demonstrated a novel approach providing candidate genes of potential clinical and biological relevance," the team says. "Immunohistochemical analyses revealed several candidates correlating with clinico-pathological factors that are markers for prostate cancer-specific survival. The impact of the candidates on prostate carcinogenesis and their potential clinical application remain to be analysed in further detailed studies."

Br J Cancer 2007; 96: 82–88


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