Mp41-20 Potential Biomarkers for Cognitive Impairment Associated With Androgen Deprivation

You have accessJournal of UrologyProstate Cancer: Markers I (MP41)1 May 2024MP41-20 POTENTIAL BIOMARKERS FOR COGNITIVE IMPAIRMENT ASSOCIATED WITH ANDROGEN DEPRIVATION Shiv Verma, Vaibhav Singh, Vijay Krishna Nagampalli, Herta Chao, and Sanjay Gupta Shiv VermaShiv Verma , Vaibhav SinghVaibhav Singh , Vijay Krishna NagampalliVijay Krishna Nagampalli , Herta ChaoHerta Chao , and Sanjay GuptaSanjay Gupta View All Author Informationhttps://doi.org/10.1097/01.JU.0001008896.93851.5b.20AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Cognitive impairment in prostate cancer patients induced, at least in part, by the second-generation androgen signaling inhibitors are frequently documented and likely have negative impacts on brain health. Such cognitive dysfunctions can affect attention, memory, language, reasoning, decision making, visuospatial function, and orientation processing speed, can persist after treatment, and their exact causes and mechanisms remain unclear. The aim of this study is to identify putative biomarkers for early diagnosis and prognosis that could stratify patients at high-risk versus no-risk of development and progression of brain deficits on androgen deprivation. METHODS: High throughput transcriptional profiling was performed in various cell culture models mimicking antiandrogen therapy. Bioinformatics analysis was performed using Advaita® iPathwayGuide and DisGeNET for identification of disease associated gene associations. Validation analysis of genes was performed by qRT-PCR assay in various human brain and prostate cancer cell lines. RESULTS: Our systematic analysis of androgen deprivation-associated genes of various biological process include neuroactive ligand-receptor interaction, axon guidance, cytokine-cytokine receptor interaction, metabolic and Hippo signaling pathways. Genes associated with neuroreceptor ligand interaction belong to ligand-gated anion channels including GABAA and B receptors whereas the nuclear core proteins were identified as the top upstream regulators. Functional enrichment and protein-protein interaction network analysis highlighted the role of ligand-gated ion channels and their receptors in cognitive brain deficits. Gene-disease association assigned forgetfulness, intellectual disability, bipolar disorder, and other neurocognitive impairment with significant overexpression of top differentially expressed genes viz. AGTR1, BDNF, GABBR2, GABRA3, GABRA5, GABRB1, GRIN1, GRIN2D, HTR1D, IFNB1, and NR3C1, respectively. Further studies in brain glial and neuronal cells, and patients undergoing androgen deprivation therapy validated these findings. CONCLUSIONS: Our study identified potential biomarkers for diagnosis of androgen deprivation-mediated brain deficits that might differentiate between men at low-risk versus high-risk of cognition. Source of Funding: Efforts are supported by the Department of Defense Grants W81XWH-19-1-0720 and W81XWH-18-1-0618 to SG © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e682 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Shiv Verma More articles by this author Vaibhav Singh More articles by this author Vijay Krishna Nagampalli More articles by this author Herta Chao More articles by this author Sanjay Gupta More articles by this author Expand All Advertisement PDF downloadLoading ...