Abstract
Objective
To investigate the genomic features of tertiary pattern 5 ( TP 5) on radical prostatectomy specimens in an effort to explain the poor clinical outcomes associated with this disease subtype.
Patients and methods
Data from 159 men with Gleason Grade Group ( GGG ) 3 or 4 were considered. All patients had Decipher diagnostic testing with transcript profiles and single-channel array normalisation (SCAN) -normalised expression of coding genes.
The relationship between Decipher and TP 5 was investigated by linear and binary logistic regressions. A differential transcriptomic analysis between patients with and without TP 5 was performed. The prognostic role of these genes on progression-free survival ( PFS ) and overall survival ( OS ) was evaluated using The Cancer Genome Atlas.
Results
In all, 52/159 (33%) patients had GGG 3–4 with TP 5 disease. TP 5 was associated with a higher Decipher score (β 0.07, 95% confidence interval [CI] 0.02–0.13; P = 0.04) and higher likelihood of falling within the intermediate- or high-risk categories ( odds ratio 3.34, 95% CI 1.34–8.35; P = 0.01). Analysis of microarray data revealed an 18-gene signature that was differentially expressed in patients with TP 5; 13 genes were over- and five under-expressed in the TP 5 cohort.
The overexpression of cyclin dependent kinase inhibitor 2B ( CDKN2B ), polo-like kinase 1 ( PLK 1 ), or cell division cycle 20 ( CDC 20 ) was associated with worse PFS . The group harbouring overexpression of at least one gene had a 5-year PFS rate of 50% vs 74% in the group without overexpression ( P < 0.001).
Conclusions
Our studies have elucidated unique genomic features of TP 5, whilst confirming previous clinical findings that patients harbouring TP 5 tend to have worse prognosis. This is the first RNA -based study to investigate the molecular diversity of TP 5 and the first correlating CDKN 2B to poorer prognosis in patients with prostate cancer.