A CD24‐p53 axis contributes to African American prostate cancer disparities. Issue 8 (13th March 2020)

• Record Type: Journal Article
• Authors: Liu, Wei; Zhang, Yue; Wei, Shi; Bae, Sejong; Yang, Wei‐Hsiung; Smith, Gary J.; Mohler, James L.; Fontham, Elizabeth T. H.; Bensen, Jeannette T.; Sonpavde, Guru P.; Chen, Guo‐Yun; Liu, Runhua; Wang, Lizhong
• Is Part Of: Prostate. Volume 80:Issue 8(2020)
• Page Start: 609
• Page End: 618
• Publication Date: 2020-03-13
• Subjects: CD24 -- metastasis -- prostate cancer -- racial disparity -- TP53; Prostate -- Diseases -- Periodicals; 616
• DOI: 10.1002/pros.23973
• Languages: English
• ISSNs: 0270-4137

Abstract

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.