Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

BRD9 Expression, Alteration, Survival And Pathway Analysis In 11 Independent Prostate Cancer Cohorts

Version 1 : Received: 3 September 2021 / Approved: 16 September 2021 / Online: 16 September 2021 (13:51:57 CEST)

How to cite: Barma, N.; Stone, T.C.; Carmona Echeverria, L.M.; Heavey, S. BRD9 Expression, Alteration, Survival And Pathway Analysis In 11 Independent Prostate Cancer Cohorts. Preprints 2021, 2021090289 (doi: 10.20944/preprints202109.0289.v1). Barma, N.; Stone, T.C.; Carmona Echeverria, L.M.; Heavey, S. BRD9 Expression, Alteration, Survival And Pathway Analysis In 11 Independent Prostate Cancer Cohorts. Preprints 2021, 2021090289 (doi: 10.20944/preprints202109.0289.v1).

Abstract

Background and aims: Despite recent advances in advanced prostate cancer treatments, there are no clinically useful biomarkers or treatments for men with such cancers. Targeted therapies have shown promise, but there remain fewer actionable targets in prostate cancer than in other cancers. This work aims to characterize BRD9, 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 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: BRD9 is overexpressed in prostate cancer patients, especially those with metastatic disease. BRD9 expression did not differ in patients treated with second generation antiandrogens versus those who were not. BRD9 is co-expressed with many genes in the SWI/SNF and BET complexes, as well as those in common signaling pathways in prostate cancer. Summary and conclusions: BRD9 has potential as a diagnostic and prognostic biomarker in prostate cancer. BRD9 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 BRD9 in vitro and in vivo, to build on the limited inhibition data available.

Keywords

BRD9; Prostate Cancer; SWI/SNF; Survival; pathways; signal transduction; human cohorts; targeted therapy

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