MP05-10 GLUCAGON-LIKE PEPTIDE-1 EXPRESSION IN PROSTATE CANCER

Field: Medicine (Health Sciences)

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology I (MP05)1 May 2024MP05-10 GLUCAGON-LIKE PEPTIDE-1 EXPRESSION IN PROSTATE CANCER Mohammed Shahait, James A. Proudfoot, Hyunnam Ryu, Elai Davicioni, Abdulrahman A. Alhajahjeh, Amman Jordan, Rayan Bater, and David I. Lee Mohammed ShahaitMohammed Shahait , James A. ProudfootJames A. Proudfoot , Hyunnam RyuHyunnam Ryu , Elai DavicioniElai Davicioni , Abdulrahman A. AlhajahjehAbdulrahman A. Alhajahjeh , Amman JordanAmman Jordan , Rayan BaterRayan Bater , and David I. LeeDavid I. Lee View All Author Informationhttps://doi.org/10.1097/01.JU.0001008740.27639.cc.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Glucagon-like peptide-1 (GLP-1) is a hormone known for its role in enhancing glucose-dependent insulin secretion. GLP-1 receptor agonists (GLP-1RA) role in managing diabetes mellitus is well established. In vitro studies showed that GLP-1RA might affect certain prostate cancer cell lines. Here, we sought to examine GLP-1R (receptor) and GCG (glucagon / GLP-1) gene expression in prostate biopsy (bx) and radical prostatectomy (RP) specimens and their correlation with baseline clinical variables as well as biologically relevant transcriptomic signatures. METHODS: De-identified baseline clinical and transcriptome data from clinical use of the Decipher test were retrieved for 116,971 bx and 52,152 RP samples from the Decipher Genomics Resource for Intelligent Discovery (GRID) database (Veracyte, Inc San Diego, CA). Associations between GLP-1 receptor (GLP1R gene) and GLP-1 (GCG gene) with baseline clinical and pathological factors and a panel of 22 transcriptomic signatures were examined by GLP-1 and GCG expression quartiles using standardized mean differences (SMD). SMD thresholds of<0.2, 0.2-0.5, and>0.7 were used to describe minimal, moderate, and large differences between groups. RESULTS: GLP1R gene expression showed minimal associations (SMD<0.2) with baseline clinical and pathological factors on both bx and RP specimens. On the other hand, there were moderate to large differences between basal-luminal subtypes in GLP1R gene expression, with the highest quartile of GLP1R expression enriched with PSC basal neuroendocrine-like subtype, PAM50 basal, lower androgen receptor (AR) activity, increased levels of a tertiary lymphoid structure (TLS) signature and decreased levels of a CD8 signature. GLP-1 (GCG gene) expression showed moderate differences between baseline clinical and pathological characteristics, with patients with the highest quartile of GCG having lower grade disease, higher likelihood of NCCN low risk tumors, and enrichment of ERG positive cases. CONCLUSIONS: Higher GLP1R gene expression was associated with basal subtype prostate cancer, lower AR activity and a more suppressed tumor immune microenvironment while higher GCG gene expression was associated with lower Gleason grade group and NCCN low risk tumors. This study lays the groundwork for clinical investigation of potential use of GLP1R agonists in the management of different facets of prostate cancer. Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e46 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Mohammed Shahait More articles by this author James A. Proudfoot More articles by this author Hyunnam Ryu More articles by this author Elai Davicioni More articles by this author Abdulrahman A. Alhajahjeh More articles by this author Amman Jordan More articles by this author Rayan Bater More articles by this author David I. Lee More articles by this author Expand All Advertisement PDF downloadLoading ...