A Systems Approach to Interrogate Gene Expression Patterns in African American Men Presenting with Clinically Localized Prostate Cancer

Gary Hardiman*, Stephen J. Savage, E. Starr Hazard, Willian A. da Silveira, Rebecca Morgan, Adam Harris, Melanie S. Jefferson, Robert C. Wilson, Susan Caulder, Linda Ambrose, Lewis Frey, Bethany Wolf, Sebastiano Gattoni-Celli, Chanita Hughes Halbert*

*Corresponding author for this work

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Abstract

An emerging theory about racial differences in cancer risk and outcomes is that psychological and social stressors influence cellular stress responses; however, limited empirical data are available on racial differences in cellular stress responses among men who are at risk for adverse prostate cancer outcomes. In this study, we undertook a systems approach to examine molecular profiles and cellular stress responses in an important segment of African American (AA) and European American (EA) men: men undergoing prostate biopsy. We assessed the prostate transcriptome with a single biopsy core via high throughput RNA sequencing (RNA-Seq). Transcriptomic analyses uncovered impacted biological pathways including PI3K-Akt signaling pathway, Neuroactive ligand-receptor interaction pathway, and ECM-receptor interaction. Additionally, 187 genes mapping to the Gene Ontology (GO) terms RNA binding, structural constituent of ribosome, SRP-dependent co-translational protein targeting to membrane and the biological pathways, translation, L13a-mediated translational silencing of Ceruloplasmin expression were differentially expressed (DE) between EA and AA. This signature allowed separation of AA and EA patients, and AA patients with the most severe clinical characteristics. AA patients with elevated expression levels of this genomic signature presented with higher Gleason scores, a greater number of positive core biopsies, elevated dehydroepiandrosterone sulfate levels and serum vitamin D deficiency. Protein-protein interaction (PPI) network analysis revealed a high degree of connectivity between these 187 proteins.
Original languageEnglish
Article number5143
JournalCancers
Volume13
Issue number20
DOIs
Publication statusPublished - 14 Oct 2021

Bibliographical note

Funding Information:
Funding: This research was funded by an NIH/NIMHD award to the Medical University of South Carolina Transdisciplinary Collaborative Center in Precision Medicine and Minority Men’s Health (U54MD010706-CHH). The authors also acknowledge support from the Genomics Shared Resource, Hollings Cancer Center, Medical University of South Carolina. This shared resource is supported in part by the Hollings Cancer Center, Medical University of South Carolina Support Grant (P30 CA 138313). All authors reviewed and approved the manuscript. G.H. acknowledges support from NIH/NIDA 1U01DA045300-01A1 and start-up funding from Queens University Belfast.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • stress
  • precision medicine
  • RNA-Seq
  • prostate
  • health disparities
  • African American
  • vitamin D
  • transcriptomics

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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