Characterizing the Activity of Inflammasome-Related Genes and Their Association With Oncological Outcomes in Prostate Cancer.

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.