Dataset Information

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

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 TP53^R175H and TP53^R273H .

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 TP53^R273H mutation was found in five cases, but no TP53^R175H 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.

SUBMITTER: Liu W

PROVIDER: S-EPMC7176538 | biostudies-literature |

REPOSITORIES: biostudies-literature

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