Abstract 4668: Prognostic significance and therapeutic potential of TOP2A expression in rare cancers

Abstract Background: TOP2A (Topoisomerase IIα) is a crucial nuclear enzyme involved in various processes of DNA metabolism, including replication, transcription, and chromosome segregation. Aberrant expression of TOP2A leads to chromosomal instability, increased cell proliferation and migration, and enhanced tumor invasiveness. Its high expression has been associated with poor prognosis in several common cancers, but its relationship with prognosis in rare cancers remains unclear. This study aims to investigate the expression, prognosis, and mechanisms of TOP2A in rare tumors using the TCGA (The Cancer Genome Atlas) bioinformatics database. The findings of this study will contribute to the understanding of targeted therapy and the molecular mechanisms underlying prognosis in these rare tumors. Methods: We utilized the TCGA datasets, comprising 80 cases of ACC, 516 cases of LGG, 120 cases of THYM, and 259 cases of SARC, to investigate the expression levels of TOP2A. A comparison between normal and tumor tissues was conducted using the Mann-Whitney test. Based on the expression levels of TOP2A, the patients were categorized into two groups: high and low. The prognostic significance of TOP2A expression in these cancer types was evaluated using Kaplan-Meier Plotter. Furthermore, the correlation between TOP2A expression and BRCA1, BRCA2, and MMR genes was assessed using the Pearson correlation coefficient. Results: Kaplan-Meier survival analysis revealed that in the overall population, the group with high expression of TOP2A exhibited significantly lower survival rates compared to the group with low expression (p < 0.05). This trend was consistently observed in ACC, LGG, and THYM cohorts. In the SARC cohort, when the threshold for TOP2A expression was set at 50%, there was no significant difference in survival between the two groups. However, a significant survival difference was observed between the top 25% and bottom 25% of TOP2A expression (p = 0.022). According to the Mann-Whitney analysis, the expression of TOP2A was significantly higher in these four cancer types compared to normal tissues. The correlation analysis between TOP2A expression and mismatch repair genes as well as homologous recombination repair genes revealed a strong association between TOP2A expression and BRCA1 and RAD51 (correlation coefficients of 0.59 and 0.8, respectively). Conclusion: The elevated expression of TOP2A in rare cancers, along with its significant correlation with tumor progression and poor prognosis, suggests its potential as a promising therapeutic target and prognostic marker for these rare malignancies. These findings provide valuable insights and a theoretical foundation for further elucidating the mechanistic role of TOP2A in the pathogenesis of these cancer types. Citation Format: Jifa Li, hua Ye, xiaoqiong Bao, wenwen Yu, xiangxiang Chen, yangyang Ni, jincong Wang, yubo Shi. Prognostic significance and therapeutic potential of TOP2A expression in rare cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4668.