Dissecting the Significance of Acid Phosphatase 1 Gene Alterations in Prostate Cancer.

Autor:	Abdallah N; Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH., Elliott A; Caris Life Sciences, Phoenix, AZ., Smith N; Caris Life Sciences, Phoenix, AZ., Stanford SM; Department of Medicine, University of California San Diego School of Medicine, La Jolla, CA., Agarwal N; Huntsman Cancer Institute, Salt Lake City, UT., Bagrodia A; Department of Urology, University of California, San Diego, La Jolla, CA., Garje R; Miami Cancer Institute, Baptist Health South Florida, Miami, FL., Bottini N; Department of Medicine, University of California San Diego School of Medicine, La Jolla, CA., McKay RR; Department of Medicine, University of California San Diego School of Medicine, La Jolla, CA.
Jazyk:	angličtina
Zdroj:	JCO precision oncology [JCO Precis Oncol] 2024 Oct; Vol. 8, pp. e2400444. Date of Electronic Publication: 2024 Oct 02.
DOI:	10.1200/PO-24-00444
Abstrakt:	Purpose: The acid phosphatase 1 ( ACP1 ) gene encodes low-molecular-weight protein tyrosine phosphatase, which is overexpressed in prostate cancer (PC) and a potential therapeutic target. We analyzed ACP1 expression in primary/metastatic PC and its association with molecular profiles and clinical outcomes. Methods: NextGen sequencing of DNA (592-gene/whole-exome sequencing)/RNA(whole-transcriptome sequencing) was performed for 5,028 specimens. ACP1 -High/ ACP1 -Low expression was defined as quartile (Q4/1) of RNA transcripts per million (TPM). DNA mutational profiles were analyzed for ACP1 -quartile-stratified samples. Gene set enrichment analysis was used for Hallmark collection of pathways. PD-L1+(≥2+, ≥5%; SP142) was tested by immunohistochemistry. Tumor microenvironment's (TME) immune cell fractions were estimated by RNA deconvolution/quanTIseq. Overall survival (OS) was assessed from initial diagnosis/treatment initiation to death/last follow-up. Results: We included 3,058 (60.8%) samples from the prostate, 634 (12.6%) from lymph node metastases (LNMs), and 1,307 (26.0%) from distant metastases (DMs). ACP1 expression was higher in LNM/DM than prostate (49.8/47.9 v 44.1 TPM; P < .0001). TP53 mutations were enriched in ACP1 -Q4 (37.9%[Q4] v 27.0%[Q1]; P < .001) among prostate samples. Pathways associated with cell cycle regulation and oxidative phosphorylation were enriched in ACP1 -Q4, whereas epithelial-mesenchymal transition and tumor necrosis factor-alpha signaling via nuclear factor kappa-light-chain-enhancer of activated B-cell pathways were enriched in ACP1 -Q1. Neuroendocrine and androgen receptor signaling was increased in ACP1 -Q4. M2 macrophages and natural killer cell fractions were increased, whereas T cells and M1 macrophages were decreased in ACP1 -Q4. While OS differences between ACP1 -Q1/Q4 were not statistically significant, there was a trend for worse OS among ACP1 -Q4 prostate samples (Q4 v Q1: hazard ratio [HR], 1.19 [95% CI, 0.99 to 1.42]; P = .06) and DM (HR, 1.12 [95% CI, 0.93 to 1.36]; P = .22) but not LNM (HR, 0.98 [95% CI, 0.74 to 1.29]; P = .87). Conclusion: ACP1-High tumors exhibit a distinct molecular profile and cold TME, highlighting ACP1 's potential role in PC pathogenesis and novel therapeutic targeting.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu