A CD24-p53 axis contributes to African American prostate cancer disparities

Academic Article

Abstract

  • Background: Using a functional analysis of prostate cancer cells, we found a CD24-dependent inactivation of mutant p53, but the clinical significance of this observation remained uncertain. Here, we validated these results with samples of human prostate cancer and explored the role of a CD24-p53 axis in racial disparities of prostate cancer. Methods: Samples of formalin-fixed, paraffin-embedded prostate cancer from 141 European Americans (EAs) and 147 African Americans (AAs) in two independent sample cohorts were assessed for protein expression of CD24, mutant p53, mouse double minute 2 human homolog (MDM2), and cyclin dependent kinase inhibitor 2A (ARF) using immunohistochemical analyses. All samples were analyzed for TP53R175H and TP53R273H. Results: CD24, mutant p53, MDM2, and ARF proteins were expressed in 55%, 24%, 39%, and 68% of prostate cancer samples, respectively. CD24 and mutant p53 were present more frequently in late-stage and metastatic prostate cancer. The presence of CD24 was associated with a greater than fourfold risk of metastasis, which included lymph node and distant metastases. H score analysis showed positive correlations of CD24 expression with mutant p53 (r =.308, P <.001) and MDM2 (r =.227, P =.004). There was a negative correlation for CD24 with ARF (r = −.280, P <.001). A racial disparity was evident for CD24 (AAs/EAs: 64% vs 47%; P =.004) but not for mutant p53 (AA/EA: 28% vs 21%; P =.152). In 32 CD24+/mutant p53+ cases, a TP53R273H mutation was found in five cases, but no TP53R175H mutation was found. Conclusion: The CD24-p53 axis may contribute to aggressive and metastatic prostate cancers, especially those of AAs. This observation enhances understanding of the pathogenesis of prostate cancer and its associated racial disparities.
  • Digital Object Identifier (doi)

    Author List

  • Liu W; Zhang Y; Wei S; Bae S; Yang WH; Smith GJ; Mohler JL; Fontham ETH; Bensen JT; Sonpavde GP
  • Start Page

  • 609
  • End Page

  • 618
  • Volume

  • 80
  • Issue

  • 8