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. 2012 Mar 13;106(6):1095-9.
doi: 10.1038/bjc.2012.39. Epub 2012 Feb 23.

Prognostic value of a cell cycle progression signature for prostate cancer death in a conservatively managed needle biopsy cohort

J Cuzick  1 , D M Berney, G Fisher, D Mesher, H Møller, J E Reid, M Perry, J Park, A Younus, A Gutin, C S Foster, P Scardino, J S Lanchbury, S Stone; Transatlantic Prostate Group
Collaborators, Affiliations

Prognostic value of a cell cycle progression signature for prostate cancer death in a conservatively managed needle biopsy cohort

J Cuzick et al. Br J Cancer. .

Abstract

Background: The natural history of prostate cancer is highly variable and it is difficult to predict. We showed previously that a cell cycle progression (CCP) score was a robust predictor of outcome in a conservatively managed cohort diagnosed by transurethral resection of the prostate. A greater need is to predict outcome in patients diagnosed by needle biopsy.

Methods: Total RNA was extracted from paraffin specimens. A CCP score was calculated from expression levels of 31 genes. Clinical variables consisted of centrally re-reviewed Gleason score, baseline prostate-specific antigen level, age, clinical stage, and extent of disease. The primary endpoint was death from prostate cancer.

Results: In univariate analysis (n=349), the hazard ratio (HR) for death from prostate cancer was 2.02 (95% CI (1.62, 2.53), P<10(-9)) for a one-unit increase in CCP score. The CCP score was only weakly correlated with standard prognostic factors and in a multivariate analysis, CCP score dominated (HR for one-unit increase=1.65, 95% CI (1.31, 2.09), P=3 × 10(-5)), with Gleason score (P=5 × 10(-4)) and prostate-specific antigen (PSA) (P=0.017) providing significant additional contributions.

Conclusion: For conservatively managed patients, the CCP score is the strongest independent predictor of cancer death outcome yet described and may prove valuable in managing clinically localised prostate cancer.

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Conflict of interest statement

Drs Lanchbury, Gutin, Stone, Mr Perry, Mr Park, Mr Younus and Ms Reid are employees of Myriad Genetics. The other authors declare no conflict of interest.

Disclaimer

The cell cycle expression profiles were assayed blind to all other data by Myriad Genetics. Analysis was conducted at QMUL under the direction of Professor Cuzick, following a predefined Statistical Analysis Plan. Interpretation of the data was done jointly by all authors, but the final content of this report was determined by non-corporate authors.

Figures

Figure 1
Figure 1
Kaplan–Meier estimates of prostate cancer death according to CCP score. Different categories of CCP score are shown by different coloured lines: red, CCP score>3 (n=16), orange, 2<CCP score ⩽3 (n=50); blue, 1<CCP score ⩽2 (n=114); purple, 0<CCP score ⩽1 (n=133); green, CCP score ⩽0 (n=36).
Figure 2
Figure 2
Ten-year predicted risk of prostate cancer death according to combined risk score, and a histogram of the combined score in different Gleason score categories. Different categories are shown by different coloured bars: blue, Gleason score <7; orange, Gleason score=7; red, Gleason score >7.
Figure 3
Figure 3
Hazard ratio for prostate cancer mortality for a one-unit change in CCP score for different clinical subgroups. The area of the box is proportional to number of events in each group, and the horizontal bars represent 95% confidence intervals (CI).
Figure 4
Figure 4
Scatter plot of predicted 10-year risk of death from prostate cancer for combined risk score vs clinical risk score. Different Gleason score categories are shown by different coloured dots: (blue, Gleason < 7; orange, Gleason=7; red, Gleason >7), whereas the vertical axis indicates the added information in PSA and the horizontal axis for PSA and CCP score. For any given patient, the added contribution of the CCP score to the predicted risk, based on Gleason and PSA, can be determined by the horizontal distance between the dot and the diagonal dashed line.
See this image and copyright information in PMC

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