Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Sterbis, J.R. et al.

Higher expression of the androgen-regulated gene PSA/HK3 mRNA in prostate cancer tissues predicts biochemical recurrence-free survival.

PURPOSE: Alterations of the androgen receptor (AR)-mediated signaling through numerous mechanisms are increasingly recognized in prostate cancer (CaP) progression. We hypothesized that the assessment of well-defined AR transcriptional targets (e.g., PSA/HK3 mRNA) in CaP tissues will provide in vivo readout of AR dysfunctions. Moreover, quantitative expression features of PSA/HK3 mRNA in prostate tumor cells may serve as a prognostic indicator of disease progression. EXPERIMENTAL DESIGN: Paired benign and malignant epithelial cells (242 specimens) were obtained from laser capture microdissection of frozen OCT-embedded tissue sections prepared from radical prostatectomy specimens of 121 patients. Quantitative expression of PSA/HK3 mRNA in the matched malignant and benign cells was analyzed by real-time reverse transcription-PCR. RESULTS: CaP cells express significantly lower PSA/HK3 mRNA levels than matched benign cells (P = 0.0133). Moreover, low PSA/HK3 mRNA expression in malignant cells was associated with increased risk of biochemical recurrence (P = 0.0217), as well as with time to recurrence (P = 0.0371), in patients with intermediate preoperative serum prostate-specific antigen levels (2-10 ng/mL). The expression of androgen-dependent genes in clinical samples correlates with each other in patients with higher expression of PSA/HK3 mRNA but not in patients with lower expression of PSA/HK3 mRNA reflecting AR pathway dysfunction. CONCLUSIONS: Our study has unraveled a novel prognostic utility of quantitative measurements of PSA/HK3 mRNA reflecting AR transcriptional activity in CaP cells, which is independent of serum prostate-specific antigen. It also has potential in stratifying subsets of patients exhibiting progressive disease associated with dampened AR transcriptional functions who may be targeted by tailored therapeutic strategies.[1]

References

Higher expression of the androgen-regulated gene PSA/HK3 mRNA in prostate cancer tissues predicts biochemical recurrence-free survival. Sterbis, J.R., Gao, C., Furusato, B., Chen, Y., Shaheduzzaman, S., Ravindranath, L., Osborn, D.J., Rosner, I.L., Dobi, A., McLeod, D.G., Sesterhenn, I.A., Srivastava, S., Cullen, J., Petrovics, G. Clin. Cancer Res. (2008) [Pubmed]

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