News Release

A multiplex assay to assess activated p300/CBP in circulating prostate tumor cells

Peer-Reviewed Publication

Impact Journals LLC

Figure 1

image: Figure 1: Optimization of circulating tumor cells (CTC) staining and validation of p300 activity. view more 

Credit: 2023 Filon et al.

“The results from this initial cohort support the integration of these biomarkers into prospective clinical trials.”

BUFFALO, NY- July 24, 2023 – A new research paper was published in Oncotarget's Volume 14 on July 20, 2023, entitled, “Development of a multiplex assay to assess activated p300/CBP in circulating prostate tumor cells.”

Reduced SIRT2 deacetylation and increased p300 acetylation activity leads to a concerted mechanism of hyperacetylation at specific histone lysine sites (H3K9, H3K14, and H3K18) in castration-resistant prostate cancer (CRPC). In this new study, researchers Mikolaj Filon, Bing Yang, Tanaya A. Purohit, Jennifer Schehr, Anupama Singh, Marcelo Bigarella, Peter Lewis, John Denu, Joshua Lang, and David F. Jarrard from the University of Wisconsin examined whether circulating tumor cells (CTCs) identify patients with altered p300/CBP acetylation. 

“In the current study, employing a novel Exclusion-based Sample Preparation (ESP) technology (9) (Supplementary Figure 1) to isolate CTCs, we evaluated p300 activity, SIRT2 expression and H3K18 acetylation in CTCs in a series of patients with sensitivity or resistance to ADT.”

CTCs were isolated from 13 advanced PC patients using Exclusion-based Sample Preparation (ESP) technology. Bound cells underwent immunofluorescent staining for histone modifying enzymes (HMEs) of interest and image capture with NIS-Elements software. Using the cBioPortal PCF/SU2C dataset, the response of CRPC to androgen receptor signaling inhibitors (ARSI) was analyzed in 50 subjects. 

Staining optimization and specificity revealed clear expression of acetyl-p300, acetyl-H3K18, and SIRT2 on CTCs (CK positive, CD45 negative cells). Exposure to A-485, a selective p300/CBP catalytic inhibitor, reduced p300 and H3K18 acetylation. In CRPC patients, a-p300 strongly correlated with its target acetylated H3k18 (Pearson’s R = 0.61), and SIRT2 expression showed robust negative correlation with a-H3k18 (R = −0.60). 

A subgroup of CRPC patients (6/11; 55%) demonstrated consistent upregulation of acetylation based on these markers. To examine the clinical impact of upregulation of the CBP/p300 axis, CRPC patients with reduced deacetylase SIRT2 expression demonstrate shorter response times to ARSI therapy (5.9 vs. 12 mo; p = 0.03). A subset of CRPC patients demonstrate increased p300/CBP activity based on a novel CTC biomarker assay. 

“With further development, this biomarker suite may be used to identify candidates for CBP/p300 acetylation inhibitors in clinical development.”
 

Read the full study: DOI: https://doi.org/10.18632/oncotarget.28477 

Correspondence to: David F. Jarrard

Email: jarrard@urology.wisc.edu 

Keywords: prostate cancer, circulating tumor cells, p300/CBP
 

About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media:

 

Sign up for free Altmetric alerts about this article: https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28477

Click here to subscribe to Oncotarget publication updates.

For media inquiries, please contact: media@impactjournals.com.

 

Oncotarget Journal Office

6666 East Quaker Str., Suite 1A

Orchard Park, NY 14127

Phone: 1-800-922-0957 (option 2)

###


Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.