Comprehensive analysis of TP53 and SPOP mutations and their impact on survival in metastatic prostate cancer

作者：Jie Zhou, Yiming Lai, Shengmeng Peng, Chen Tang, Yongming Chen, Lingfeng Li, Hai Huang, Zhenghui Guo · 发表于：Frontiers in Oncology · 年份：2022 · DOI：10.3389/fonc.2022.957404 · 被引用次数：19 · 研究领域：Prostate Cancer Treatment and Research、Prostate Cancer Diagnosis and Treatment、Cancer, Lipids, and Metabolism

Background: Although TP53 and SPOP are frequently mutated in metastatic prostate cancer (PCa), their prognostic value is ambiguous, and large sample studies are lacking, especially when they co-occur with other genetic alterations. Methods: Genomic data and patients' clinical characteristics in PCa were downloaded from the cBioPortal database. We extensively analyzed other gene alterations in different mutation status of TP53 and SPOP. We further subdivided TP53 and SPOP mutation into subgroups based on different mutation status, and then evaluated the prognostic value. Two classification systems for TP53 survival analysis were used. Results: A total of 2,172 patients with PCa were analyzed in our study, of which 1,799 were metastatic PCa patients. The mutual exclusivity analysis showed that TP53 and SPOP mutation has a strong mutual exclusion (p<0.001). In multivariable analysis, truncating TP53 mutations (HR=1.773, 95%CI:1.403-2.239, p<0.001) and other TP53 mutations(HR=1.555, 95%CI:1.267-1.908, p<0.001) were independent negative prognostic markers in metastatic PCa, whereas SPOP mutations(HR=0.592, 95%CI:0.427-0.819, p<0.001) were an independent prognostic factor for better prognosis. Mutations in TP53 were significantly associated with wild-type status for SPOP and CDK12, structural variants/fusions for TMPRSS2 and ERG, AR amplification and PTEN deletion (p<0.001). And truncating TP53 mutations have higher AR amplification rates than other TP53 mutations (p=0.022). Consis...