Characterizing the Activity of Inflammasome-Related Genes and Their Association With Oncological Outcomes in Prostate Cancer.
Date
2026-05
Journal Title
Journal ISSN
Volume Title
Repository Usage Stats
views
downloads
Citation Stats
Attention Stats
Abstract
Background
Inflammation plays a critical role in cancer cell proliferation; however, the specific role of inflammasomes, multiprotein complexes that regulate inflammation-associated signaling pathways, in prostate cancer (PCa) remains insufficiently explored. This study aims to characterize the expression of inflammasome-related genes in PCa and evaluate their association with clinical outcomes.Methods
De-identified transcriptome data from the Decipher GRID RP, a cohort of 52,266 radical prostatectomy (RP) samples tested (2016-2024) with the Decipher prostate genomic classifier (Veracyte, San Diego, CA), were retrieved from the GRID registry (NCT02609269). Expression analysis of 34 genes involved in inflammatory pathways was conducted to associate their expression with clinical and genomic variables. Outcomes analyses were conducted on a retrospective cohort of 855 patients treated with RP (META855).Results
Analysis of inflammasome gene expression in the GRID RP cohort revealed that most genes exhibit low baseline expression, whereas HSP90AB1, APP, TXN, and TXNIP demonstrate strong expression signals. Additionally, higher expression of most genes was associated with Gleason Grade Group 4-5 and very high Decipher scores. On survival analysis of the META855 cohort, higher expressions of AIM2 and HSP90AB1 were significantly associated with worse metastasis-free survival. Conversely, both high and low expression levels of NLRP3 were associated with better metastasis-free survival outcomes following RP compared to average expression. On multivariable Cox regression analysis, higher expressions of AIM2 (HR 1.75) and HSP90AB1 (HR 1.60) were significantly associated with shorter time to metastasis following RP.Conclusions
There is molecular heterogeneity within pro-inflammatory genes among patients with PCa. Our findings showed there is a potential association between the expression levels of certain inflammasomes, such as AIM2, HSP90AB1, and NLRP3, and oncological outcomes following RP.Type
Department
Description
Provenance
Subjects
Citation
Permalink
Published Version (Please cite this version)
Publication Info
Ghoreifi, Alireza, Mohammed Alshalalfa, Elai Davicioni, Daniel E Spratt, R Jeffrey Karnes, J Todd Purves, Francis M Hughes, Judd W Moul, et al. (2026). Characterizing the Activity of Inflammasome-Related Genes and Their Association With Oncological Outcomes in Prostate Cancer. The Prostate. 10.1002/pros.70202 Retrieved from https://hdl.handle.net/10161/34792.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
Collections
Scholars@Duke
Monty Hughes
Dr. Hughes received his Ph.D. from the Medical University of South Carolina and was a post doc at both the University of North Carolina at Chapel Hill and NIH. He then joined the faculty of the University of North Carolina at Charlotte where he rose to the rank of Associate Professor (with tenure). Following a brief stint as the director of the biology division of a start-up pharmaceutical company, he joined forces with Dr. Purves at the Medical University of South Carolina to begin this lab focused on benign urinary disorders. Dr. Hughes has been at Duke since 2015. He is currently an Assistant Professor working within the Department of Surgery and Division of Urology. He serves as the Director of the Urinary Dysfunction Laboratory which studies the role of inflammation in disorders such as bladder outlet obstruction and diabetic bladder dysfunction. In association with Dr. J Todd Purves, this lab has been instrumental in demonstrating the central importance of the NLRP3 inflammasome in sensing the biochemical stressors associated with these disorders and translating them into an inflammatory signal. This signal is ultimately responsible for changes in voiding function, denervation and fibrosis.
Judd Wendell Moul
Dr Judd Moul joined the Duke faculty in mid 2004 after a career in the US Army Medical Corps mainly at Walter Reed Army Medical Center. He is a retired colonel and a noted researcher and clinician in the area of prostate cancer and is a urologic oncologist. He served as the division chief of Duke Division of Urology from 2004 to 2011 and was named the James H Semans MD Professor of surgery in 2009 becoming Duke's first named endowed chair for urology. He was awarded the Gold Cystoscope Award from the American Urologic Association as well as Castle Connelly Physician of the year for Clinical Medicine in 2009. He has performed more than 1300 radical prostatectomies since joining the Duke faculty and is committed to outcomes research on this series and in other areas of prostate cancer. He served as the Editor for Prostate Cancer and Prostatic Dissease, a Nature Medicine journal, for more than a decade and is a popular speaker and lecturer having been visiting professor and keynote speaker throughout the US and the World. He is very committed to training residents and mentoring students and trainees.
Michael R Abern
Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.