Pd42-06 CXC Motif Chemokine Receptor as a Differential Biomarker in Racial Disparities of Prostate Cancer

You have accessJournal of UrologyProstate Cancer: Markers II (PD42)1 May 2024PD42-06 CXC MOTIF CHEMOKINE RECEPTOR AS A DIFFERENTIAL BIOMARKER IN RACIAL DISPARITIES OF PROSTATE CANCER Amel A. Ahmed, Shiv Verma, Ibrahim M. Atawia, Daniel L. Shen, Gregory T. MacLennan, Pingfu Fu, and Sanjay Gupta Amel A. AhmedAmel A. Ahmed , Shiv VermaShiv Verma , Ibrahim M. AtawiaIbrahim M. Atawia , Daniel L. ShenDaniel L. Shen , Gregory T. MacLennanGregory T. MacLennan , Pingfu FuPingfu Fu , and Sanjay GuptaSanjay Gupta View All Author Informationhttps://doi.org/10.1097/01.JU.0001008560.54103.65.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate cancer exhibits a significant racial disparity with remarkable higher incidence and mortality rates in African-American (AA) men as compared to the Caucasian-American (CA) men. Current predictive models rely on clinical variables but do not account for these disparities. This study aims to construct a race-specific prostate cancer prognostic prediction model for risk assessment. METHODS: We conducted a comprehensive bioinformatics analysis using the data from 17 pairs of gene expression array and identified 63 differentially expressed genes (DEGs) by race. Among them, chemokine receptor 4 (CXCR4), viz. p-Akt (Ser473), fatty acid synthase (FASN), interleukin-6 (IL-6) and matrix metallopeptidase 9 (MMP-9) gene expressions were significantly altered in AA groups. Immunohistochemistry was performed on 163 prostate cancer patient specimens to validate DEG expression and Immunoreactive scores (IRS) were calculated. We further investigated the impact of these genes on biochemical recurrence-free survival (BCRFS) using Kaplan–Meier analysis to examine the differences between low-risk versus high-risk groups. RESULTS: Our data revealed that CXCR4 exhibited significantly higher expression in AA tumors, with >85% of AA prostate tumors showing weak to strong CXCR4 expression, compared to <5% in CA specimens. While Immunostaining for IL-6, FASN, MMP9 and p-Akt did not provide a significant distinction between CA and AA cases. IRS analysis confirmed the higher expression of CXCR4 in AA cancers, compared to CA prostate cancer (p<0.001). MMP9 and IL6 expression were moderately higher in AA cancer compared to CA prostate cancer (p<0.05). In contrast, FASN expression was significantly higher in CA cancer, compared to AA prostate cancer (p<0.001). BCRFS analysis demonstrated that CXCR4 is a determinant factor of recurrence risk in AA prostate cancer patients. The activation of the PI3K-Akt signaling pathway, particularly in AA patients, suggests its role in prostate cancer aggressiveness. CONCLUSIONS: This study demonstrates the importance of differential expression of biomarkers which constitute the bulk tumors in driving cancer. The distinct gene expression patterns, especially the upregulation of CXCR4, in AA prostate cancer highlight its potential as a prognostic biomarker and a target for personalized treatment strategies. These findings motivate further study into the role of population-specific difference in adding CXCR4 in risk model construction, especially in machine learning models. 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: e894 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Amel A. Ahmed More articles by this author Shiv Verma More articles by this author Ibrahim M. Atawia More articles by this author Daniel L. Shen More articles by this author Gregory T. MacLennan More articles by this author Pingfu Fu More articles by this author Sanjay Gupta More articles by this author Expand All Advertisement PDF downloadLoading ...