Abstract:
OBJECTIVES:ERG-gene rearrangement defines a distinct molecular subtype of PCA with potential biological and clinical implications. To identify a molecular signature reflective of the downstream effects of ERG-mediated transcriptional regulation with prognostic implication in patients with prostate cancer (PCA). MATERIAL AND METHODS:We used a singular value decomposition (SVD) bioinformatics approach to re-analyse gene expression data previously generated from 46 prostate tumours, and identified an ERG-like gene signature. The signature was validated on several patient cohorts and individual genes were correlated to ERG expression and PCA progression. RESULTS:An ERG-like 10-gene signature was identified and validated in PCA cohorts of the physician health study (p115) (n = 110) in addition to three independent public datasets, and was significantly associated with disease progression, biochemical recurrence and PCA-specific mortality. Patients with the ERG-like signature were significantly associated with disease recurrence on univariate (hazard ratio [HR] 2.6; 95% confidence interval [CI]:1.3-5.2; P = 0.004) and multivariate analysis (HR 2.3; 95% CI:1.1-4.6, P = 0.016) compared with patients without this signature. Within the group of patients with Gleason score (GS) 6 and 7 PCA, the signature added prognostic value beyond GS and identified patients at higher risk of cancer deaths more accurately than GS alone or in combination with ERG status. Protein expression of the 10 genes were significantly associated with ERG and disease progression regardless of ERG status. CONCLUSION:The characterized ERG-like signature was reflective of aggressive features of ERG-mediated transcription and was prognostically robust. The combination of this signature with clinicopathological variables should be validated prospectively to explore its clinical utility in stratifying patients with PCA and in identifying those at higher risk of metastatic and lethal disease.
journal_name
BJU Intjournal_title
BJU internationalauthors
Bismar TA,Alshalalfa M,Petersen LF,Teng LH,Gerke T,Bakkar A,Al-Mami A,Liu S,Dolph M,Mucci LA,Alhajj Rdoi
10.1111/bju.12262subject
Has Abstractpub_date
2014-02-01 00:00:00pages
309-19issue
2eissn
1464-4096issn
1464-410Xjournal_volume
113pub_type
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journal_title:BJU international
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journal_title:BJU international
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doi:10.1046/j.1464-410x.2000.00771.x
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journal_title:BJU international
pub_type: 杂志文章
doi:10.1111/j.1464-410X.2005.05641.x
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pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
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更新日期:2006-05-01 00:00:00
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pub_type: 杂志文章
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更新日期:2010-02-01 00:00:00
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doi:10.1111/j.1464-410X.2011.10210.x
更新日期:2011-10-01 00:00:00
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更新日期:2009-02-01 00:00:00
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更新日期:2006-10-01 00:00:00
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更新日期:2011-04-01 00:00:00
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更新日期:2004-10-01 00:00:00
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更新日期:2009-05-01 00:00:00