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A transcriptomic signature of tertiary Gleason 5 predicts worse clinicopathological outcome
Author(s) -
Martini Alberto,
Wang Joanna,
Brown Nicholas M.,
Cumarasamy Shivaram,
Sfakianos John P.,
Rastinehad Ardeshir R.,
Haines Kenneth G.,
Wiklund Nils Peter,
Nair Sujit S.,
Tewari Ashutosh K.
Publication year - 2019
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/bju.14740
Subject(s) - decipher , confidence interval , odds ratio , medicine , transcriptome , oncology , microarray , microarray analysis techniques , logistic regression , gene , biology , survival analysis , gene expression , bioinformatics , genetics
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 ( CDKN 2B ), 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.