APUC-6 Genes as a Potential Prognostic and Predictive Biomarker in the CHAARTED Prostate Cancer Trial.

Authors

Xiaolei Shi, Amol C Shetty, Jarey Wang, Yang Song, Philip A Sutera, Matthew P Deek, Krishnan R Patel, Ravi A Madan, Chad Tang, James Proudfoot, Elai Davicioni, Arif Hussain, Paul Nguyen, Christopher Sweeney, Ella Boytim, Kristine P Lacuna, Charles J Ryan, Emmanuel S Antonarakis, Phuoc T Tran, Justin Hwang

Published in

JCO precision oncology. Volume 10. Issue 8. Pages e2501012. Epub Aug 21, 2026.

Abstract

A six-gene panel involved in androgen production, uptake, and conversion (APUC-6: HSD3B1, HSD3B2, CYP3A43, CYP11A1, CYP11B1, CYP17A1) may define distinct clinical outcomes in metastatic prostate cancer. This study evaluated the prognostic and predictive value of APUC-6 expression in metastatic castration-sensitive prostate cancer (mCSPC).
Transcriptomic data from 160 patients in the phase III Eastern Cooperative Oncology Group-ACRIN E3805 CHAARTED trial were analyzed. Patients were stratified into four subgroups based on APUC-6 and androgen receptor (AR) gene expression. Clinical outcomes including time to clinical progression (ttCP), time to castration resistance (ttCR), and overall survival (OS) were assessed within the androgen deprivation therapy (ADT) and docetaxel plus ADT (D-ADT) arms. Interaction testing evaluated the predictive value of APUC-6/AR status. Subgroup analyses were also performed by Decipher genomic risk.
Patients with APUC-6-high/AR-low expression showed significantly improved ttCP (hazard ratio [HR], 0.43 [95% CI, 0.22 to 0.82]; P = .0092), ttCR (HR, 0.56 [95% CI, 0.32 to 1]; P = .049), and OS (HR, 0.31 [95% CI, 0.16 to 0.61]; P = .0003), but did not appear to benefit from the addition of docetaxel. Conversely, APUC-6-low/AR-low patients demonstrated significantly improved outcomes with D-ADT (ttCP: HR, 0.37 [95% CI, 0.21 to 0.65]; P = .00036; ttCR: HR, 0.38 [95% CI, 0.23 to 0.64]; P = .00017; OS: HR, 0.39 [95% CI, 0.21 to 0.72]; P = .0019). Statistical interaction analysis supported that patients with APUC-6-low/AR-low expression were more likely to benefit from docetaxel (HR, 0.36 [95% CI, 0.19 to 0.66]; P = .001). For patients with a high Decipher genomic classifier score, those in the APUC-6-low subgroup had improved survival with D-ADT, whereas those in the APUC-6-high subgroup did not gain any additional benefit from docetaxel.
APUC-6 expression and AR gene expression define clinically relevant subgroups in mCSPC and may enhance precision medicine treatment approaches in combination with other transcriptomic biomarkers.

PMID:
42628007
Bibliographic data and abstract were imported from PubMed on 22 Aug 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.