George Washington University School of Medicine and Health Sciences, Washington DC, DC
Jennifer Kate Beckerman , Claire Valburg , Ramesh Subrahmanyam , Victor Nava , Alexandra Zara Rozalen , Guoqing Diao , Shanshan Liu , Martha Antonio , Maneesh Rajiv Jain
Background: XIAP acts in both the extrinsic and intrinsic apoptotic pathways as an inhibitor of cell death, protecting cells from a range of triggers. Regulation due to apoptosis resistance may represent a targetable factor for therapeutic intervention in prostate cancer. This study focuses on XIAP as a biomarker and its expression in correlation with disease aggression. Methods: Expression levels of XIAP was analyzed by immunohistochemistry (IHC), graded 1 through 3 according to signal intensity, in radical prostatectomy samples from 90 patients with prostate cancer with a range of phenotypes including: indolent (A), locally advanced (B), progressive to metastatic (C) and de novo metastatic (D). Prognostic data was collected and Fisher’s exact statistical analysis was performed. Secondary analyses included a Fisher’s exact test with a pairwise comparison between individual disease grades and Gleason scores. Results: Higher XIAP protein expression levels on IHC correlated with disease grade and with total Gleason score (p = 0.0008 and p = 0.0002 respectively) by Fisher’s exact test analysis, indicating more aggressive disease phenotypes. Secondary results looked at a pairwise Fisher’s exact analysis comparing XIAP expression levels among disease grades (A-D) and Gleason scores. XIAP expression only significantly differed between those with grade A and D as well as between individuals with grades B and D (measured by Bonferroni-adjusted p-value of 0.003 and 0.018 respectively). Statistical significance was also achieved in XIAP expression levels when comparing among Gleason scores 6 and 8 (p = 0.025), 6 and 9 (p = 0.0125), as well as 7 and 9 (p = 0.030). Conclusions: This study demonstrates a correlation between XIAP expression levels by IHC and aggressiveness of disease, demonstrating clinical significance of XIAP as a prostate cancer biomarker.
XIAP grade, N (%) | 1 | 2 | 3 | |
---|---|---|---|---|
Disease grade | ||||
Indolent (A) | 30 | 6 (20) | 18 (60) | 6 (20) |
Locally advanced (B) | 30 | 4 (13.3) | 16 (53.3) | 10 (33.3) |
Metastatic, Progressed (C) | 18 | 0 (0) | 9 (50) | 9 (50) |
Metastatic, De Novo (D) | 12 | 0 (0) | 1 (8.3) | 11 (91.7) |
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