Cell cycle progression is ‘robust’ prognostic marker for prostate cancer
MedWire News: Levels of expression of cell cycle progression (CCP) genes - those that encourage cell growth - could have an essential role in determining the appropriate treatment for patients with prostate cancer, say researchers.
The team shows that a CCP "score" can predict the likelihood of biochemical recurrence in men who have already undergone radical prostatectomy, and can improve the prediction of time to death compared with any other clinical variable in men who are being treated with active surveillance.
"Therefore, addition of the CCP score to clinical variables allows more accurate prediction of which men can be safely managed by watchful waiting, and, of equal importance, which men with apparently low-risk disease actually are at high risk of death from prostate cancer and might benefit from medical treatment," suggest Jack Cuzick (Queen Mary University of London, UK) and colleagues.
The group measured the expression of 31 genes involved in CCP using reverse transcriptase-polymerase chain reaction on RNA in tissue samples from 366 US prostatectomy patients, and 337 UK men with clinically localized prostate cancer who had undergone transurethral resection of the prostate (TURP) and were being treated conservatively.
Patients in the former cohort were followed-up for a median period of 9.4 years, and every 1-unit increase in CCP score (denoting the expression-level of CCP genes per patient) increased the risk for biochemical recurrence - defined as a prostate-specific antigen (PSA) concentration greater than 0.3 ng/ml - 1.89-fold.
Furthermore, after accounting for clinical variables including diagnostic Gleason score, most recent prebiopsy PSA concentration, and clinical disease stage, CCP score (1-unit increase) and PSA level were the most significant predictors of recurrence, with hazard ratios (HRs) of 1.74 and 1.98, respectively.
After a median follow-up duration of 9.8 years in the UK TURP cohort, 51% of men had died, 20% from prostate cancer, and 31% from other causes.
Compared with the prostatectomy cohort, the CCP score correlated more positively with Gleason score, PSA concentration, Ki67 (percentage of positive cells), and extent of disease in the TURP cohort, report Cuzick et al in the Lancet Oncology.
Indeed, after adjustment for all of these variables, CCP score remained a strong prognostic indicator?, conferring a 2.57-fold increase in the risk for death from prostate cancer per 1-unit increase among the TURP patients.
"Our findings have great potential," concluded Cuzick, lead author of the study.
"CCP genes are expressed at higher levels in actively growing cells, so we could be indirectly measuring the growth rate and inherent aggressiveness of the tumor through our test," he added.
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By Sarah Guy