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Comparative Genomics Reveals Distinct Immune-oncologic Pathways in African American Men with Prostate Cancer

Shivanshu Awasthi1, Anders Berglund2, Julieta Abraham-Miranda1

  • 1Department of Cancer Epidemiology, H Lee Moffitt Cancer Center & Research Institutes, Tampa, Florida.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|October 10, 2020
PubMed
Abstract

Insights

African American men with prostate cancer show distinct immune profiles, with heightened inflammation linked to worse outcomes. Understanding these immune-oncologic differences can guide personalized treatment strategies for better prostate cancer care.

Area of Science:

  • Oncology
  • Immunology
  • Genomics

Background:

  • Racial disparities in prostate cancer outcomes persist, with limited understanding of the underlying immune-oncologic mechanisms.
  • Investigating molecular differences in the tumor microenvironment between African American men (AAM) and European American men (EAM) is crucial.

Purpose of the Study:

  • To evaluate immune-oncologic differences in the prostate tumor microenvironment between AAM and EAM.
  • To identify specific immune-related genes and pathways associated with racial disparities in prostate cancer.

Main Methods:

  • Analysis of whole transcriptome data from 1,173 radical prostatectomy samples.
  • Selection and assessment of 1,260 immune-specific genes for differential expression.
  • Pathway analysis using gene set enrichment and intergene correlational matrices.

Main Results:

  • AAM prostate tumors exhibit significant enrichment of proinflammatory pathways (cytokines, IFN, TNFα, ILs) and epithelial-mesenchymal transition.
  • AAM tumors show a higher immune content score and are genomically radiosensitive with lower DNA damage repair compared to EAM.
  • Overexpression of IFITM3 in AAM tumors predicts increased risk of biochemical recurrence, but not in EAM.

Conclusions:

  • Prostate tumors in AAM display a unique immune profile characterized by enriched proinflammatory pathways, correlating with poorer outcomes.
  • These immune-oncologic disparities suggest the need for genomically adaptive treatment approaches for AAM prostate cancer patients.

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