Department of Genetics and O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama.
Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama.
Prostate. 2020 May;80(8):609-618. doi: 10.1002/pros.23973. Epub 2020 Mar 13.
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.
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 and TP53 .
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 mutation was found in five cases, but no TP53 mutation was found.
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.
通过对前列腺癌细胞的功能分析，我们发现 CD24 依赖性失活突变型 p53，但这一观察结果的临床意义尚不确定。在这里，我们使用人类前列腺癌样本验证了这些结果，并探讨了 CD24-p53 轴在前列腺癌种族差异中的作用。
在两个独立的样本队列中，使用免疫组织化学分析评估了 141 例欧洲裔美国人（EA）和 147 例非裔美国人（AA）的福尔马林固定、石蜡包埋前列腺癌样本中 CD24、突变型 p53、鼠双微体 2 人类同源物（MDM2）和细胞周期蛋白依赖性激酶抑制剂 2A（ARF）的蛋白表达。所有样本均进行 TP53 和 TP53 分析。
CD24、突变型 p53、MDM2 和 ARF 蛋白在分别在 55%、24%、39%和 68%的前列腺癌样本中表达。CD24 和突变型 p53 在晚期和转移性前列腺癌中更为常见。CD24 的存在与转移的风险增加四倍以上相关，包括淋巴结和远处转移。H 评分分析显示 CD24 表达与突变型 p53（r =.308，P <.001）和 MDM2（r =.227，P =.004）呈正相关。CD24 与 ARF 呈负相关（r =.280，P <.001）。CD24 存在种族差异（AA/EA：64%比 47%；P =.004），但突变型 p53 无差异（AA/EA：28%比 21%；P =.152）。在 32 例 CD24 /突变型 p53 病例中，发现 5 例存在 TP53 突变，但未发现 TP53 突变。
CD24-p53 轴可能导致侵袭性和转移性前列腺癌，尤其是非裔美国人的前列腺癌。这一观察结果增强了对前列腺癌发病机制及其相关种族差异的理解。
