ArticleJNCI cancer spectrum2025
Multi-gene risk score for prediction of clinical outcomes in treatment-naïve metastatic castrate-resistant prostate cancer.
Article in JNCI cancer spectrum, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Web-based application of integrated clinico-genomic prognostic nomograms in metastatic castration-resistant prostate cancer.The journal of liquid biopsy · 2026Article
- Clinico-genomic risk stratification for biomarker-enriched trial design in poor-prognosis metastatic castrate-resistant prostate cancer (mCRPC).The journal of liquid biopsy · 2026Article
- Clinico-genomic nomograms for estimation of survival risk in metastatic castrate-resistant prostate cancer.JNCI cancer spectrum · 2026Article
- Uncovering the role of ETS2 in prostate cancer pathogenesis: relationship with p53 and ERG.Molecular biology reports · 2026Article
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Authors and funding
10 authors.
Funding
Abstract
backgroundTo determine the performance of a multi-gene copy number variation (MG-CNV) risk score in metastatic tissue and plasma biospecimens from treatment-naïve metastatic castration-resistant prostate cancer (mCRPC) patients for prediction of clinical outcomes.
methodsThe mCRPC tissue and plasma cell-free DNA (cfDNA) biospecimen sequencing results obtained from publicly accessed cohorts in dbGaP, cBioPortal, and an institutional mCRPC cohort were used to develop a MG-CNV risk score derived from gains in AR, MYC, COL22A1, PIK3CA, PIK3CB, NOTCH1 and losses in TMPRSS2, NCOR1, ZBTB16, TP53, NKX3-1 in independent cohorts for determining overall survival (OS), progression-free survival (PFS) to first-line androgen receptor pathway inhibitors (ARPIs). The range of the risk scores for each cohort was dichotomized into "high-risk" and "low-risk" groups and association with OS/PFS determined. Univariate and multivariable Cox proportional hazards regressions were applied for survival analyses (P < .05 for statistical significance).
resultsOf 1137 metastatic tissue-plasma biospecimens across all cohorts, 699/1137 were treatment-naive mCRPC (235/699 metastatic tissue; 464/699 plasma-cfDNA), and 311/1137 were matched tissue-cfDNA pairs. In multivariable analysis, the MG-CNV risk score derived from metastatic tissue or in cfDNA was statistically significantly associated with OS with high score associated with short survival (hazard ratio = 2.65, confidence interval = 1.99 to 3.51; P = 1.35-11) and shorter PFS to ARPIs (median PFS of 7.8 months) compared with 14 months in patients with low-risk score.
conclusionsA molecular risk score in treatment-naïve mCRPC state obtained either in metastatic tissue or cfDNA predicts clinical survival outcomes and offers a tumor biology-based tool to design biomarker-based enrichment clinical trials.
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