Exploring the Value of <i>BRD9</i> as a Biomarker, Therapeutic Target and Co-Target in Prostate Cancer

Background and aims: Despite recent advances in advanced prostate cancer treatments, clinical biomarkers or treatments for men with such cancers are imperfect. Targeted therapies have shown promise, but there remain fewer actionable targets in prostate cancer than in other cancers. This work aims to...

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Bibliographic Details
Main Authors: Nafisa Barma, Timothy C. Stone, Lina Maria Carmona Echeverria, Susan Heavey
Format: Article
Language:English
Published: MDPI AG 2021-11-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/11/12/1794
Description
Summary:Background and aims: Despite recent advances in advanced prostate cancer treatments, clinical biomarkers or treatments for men with such cancers are imperfect. Targeted therapies have shown promise, but there remain fewer actionable targets in prostate cancer than in other cancers. This work aims to characterise <i>BRD9</i>, currently understudied in prostate cancer, and investigate its co-expression with other genes to assess its potential as a biomarker and therapeutic target in human prostate cancer. Materials and methods: Omics data from a total of 2053 prostate cancer patients across 11 independent datasets were accessed via Cancertool and cBioPortal. mRNA M.expression and co-expression, mutations, amplifications, and deletions were assessed with respect to key clinical parameters including survival, Gleason grade, stage, progression, and treatment. Network and pathway analysis was carried out using Genemania, and heatmaps were constructed using Morpheus. Results: <i>BRD9</i> is overexpressed in prostate cancer patients, especially those with metastatic disease. <i>BRD9</i> expression did not differ in patients treated with second generation antiandrogens versus those who were not. <i>BRD9</i> is co-expressed with many genes in the SWI/SNF and BET complexes, as well as those in common signalling pathways in prostate cancer. Summary and conclusions: <i>BRD9</i> has potential as a diagnostic and prognostic biomarker in prostate cancer. <i>BRD9</i> also shows promise as a therapeutic target, particularly in advanced prostate cancer, and as a co-target alongside other genes in the SWI/SNF and BET complexes, and those in common prostate cancer signalling pathways. These promising results highlight the need for wider experimental inhibition and co-targeted inhibition of <i>BRD9</i> in vitro and in vivo, to build on the limited inhibition data available.
ISSN:2218-273X