RT Journal Article
SR Electronic
T1 Positive STAT5 protein and locus amplification status predicts recurrence after radical prostatectomy to assist clinical precision management of prostate cancer
JF Cancer Epidemiology Biomarkers & Prevention
JO Cancer Epidemiol Biomarkers Prev
FD American Association for Cancer Research
SP cebp.1358.2018
DO 10.1158/1055-9965.EPI-18-1358
A1 Haddad, Bassem R.
A1 Erickson, Andrew
A1 Udhane, Vindhya
A1 LaViolette, Peter S
A1 Rone, Janice D.
A1 Kallajoki, Markku A
A1 See, William A.
A1 Rannikko, Antti
A1 Mirtti, Tuomas
A1 Nevalainen, Marja T
YR 2019
UL http://cebp.aacrjournals.org/content/early/2019/07/10/1055-9965.EPI-18-1358.abstract
AB Background: A significant fraction of prostate cancer (PC) patients experience post-radical prostatectomy (RP) biochemical-recurrence (BCR). New predictive markers are needed for optimizing post-operative PC management. STAT5 is an oncogene in PC which undergoes amplification in 30% of PCs during progression. Methods: We evaluated the significance of positive status for nuclear STAT5 protein expression vs. STAT5 locus amplification vs. combined positive status for both in predicting BCR after RP in 300 patients. Results: Combined positive STAT5 status was associated with 45% disadvantage in BCR in Kaplan-Meier survival analysis in all Gleason grade patients. Patients with Gleason-grade groups (GG) 2 and 3 PCs and combined positive status for STAT5 had a more pronounced disadvantage of 55-60% at 7 years after RP in univariate analysis. In multivariate analysis including the CAPRA-S nomogram variables, combined positive STAT5 status was independently associated with a shorter BCR-free survival in all Gleason GG patients (HR=2.34, p=0.014) and in intermediate Gleason GG 2 or 3 patients (HR=3.62, p=0.021). The combined positive STAT5 status improved the predictive value of the CAPRA-S nomogram in both ROC-AUC analysis and in decision-curve-analysis for BCR. Conclusions: Combined positive status for STAT5 was independently associated with shorter disease-free survival in univariate analysis and was an independent predictor for BCR in multivariate analysis using the CAPRA-S variables in PC. Impact: Our results highlight potential for a novel precision medicine based on pivotal role of STAT5 status in improving selection of PC patients who are candidates for early adjuvant interventions to reduce the risk of recurrence.