Abstract 778: CD24 mutant p53 contribute to racial disparities in prostate cancer

Abstract

Abstract African-American (AA) men have the highest rate of prostate cancer among racial or ethnic groups. CD24, a cell-surface protein anchored by glycosyl-phosphatidyl-inositol (GPI), often is over-expressed in cancers and serves as a marker for poor prognosis of human cancer, including prostate cancer. 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. Our bioinformatics analysis of public datasets, including TCGA data, confirmed higher levels of CD24 mRNA expression in late-stage and metastatic prostate cancer. In the present study, we addressed the association of CD24 with mutant p53 and their differential expression between AA and European-American (EA) prostate cancers and assessed whether cells with CD24 and mutant p53 contribute to health disparities in prostate cancer. 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 > 4-fold risk of metastasis, which included lymph node and distant metastases. H-score analysis showed positive correlations of CD24 expression with mutant p53 and MDM2. A racial disparity was evident for CD24 but not for mutant p53. In 32 CD24+/mutant p53+ cases, a TP53R273H mutation was found in five cases, but no TP53R175H mutation was found. The CD24-p53 axis may contribute to aggressive and metastatic prostate cancers, especially those of AAs. Citation Format: Xuelian Cui, Shuaibin Wang, Lizhong Wang. CD24 mutant p53 contribute to racial disparities in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 778.