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Prognostic and Therapeutic Implications of Cell Division Cycle 20 Homolog in Breast Cancer

S. Messeha,N. Zarmouh,Henrietta Maku,S. Gendy,Clement G Yedjou,Rashid I. Elhag,L. Latinwo,Caroline O Odewumi,K. Soliman

Published 2024 in Cancers

ABSTRACT

Simple Summary In breast cancer (BC), the triple-negative breast cancer subtype, the upregulation of CDC20 is positively associated with cancer initiation, progression, metastasis, and chemotherapy resistance. The current functional enrichment analysis study demonstrated the significant association of CDC20 co-expressed genes with biological regulation and cellular processes. This study reveals a significant positive correlation between overexpressed CDC20 and tumor purity and many immune cells; the finding suggests that CDC20 plays a fundamental role in controlling tumor immunity and consequently influences BC prognosis. CDC20 deficiency led to decreased cell growth and metastasis, G2/M cell cycle arrest, and boosted the cytotoxic effects of paclitaxel treatment, which supports the current analysis. Developing natural and synthetic inhibitors of this oncogene is a promising approach to the therapeutic management of BC. Abstract Cell division cycle 20 homolog (CDC20) is a well-known regulator of cell cycle progression. Abnormal expression of CDC20 leads to mitotic defects, which play a significant role in cancer development. In breast cancer (BC), CDC20 has been identified as a biomarker that has been linked to poor patient outcomes. In this study, we investigated the association of CDC20 with BC prognosis and immune cell infiltration by using multiple online databases, including UALCAN, KM plotter, TIMER2.0, HPA, TNM-plot, bc-GenExMiner, LinkedOmics, STRING, and GEPIA. The results demonstrate that BC patients have an elevated CDC20 expression in tumor tissues compared with the adjacent normal tissue. In addition, BC patients with overexpressed CDC20 had a median survival of 63.6 months compared to 169.2 months in patients with low CDC20 expression. Prognostic analysis of the examined data indicated that elevated expression of CDC20 was associated with poor prognosis and a reduction of overall survival in BC patients. These findings were even more prevalent in chemoresistance triple-negative breast cancer (TNBC) patients. Furthermore, the Gene Set Enrichment Analysis tool indicated that CDC20 regulates BC cells’ cell cycle and apoptosis. CDC20 also significantly correlates with increased infiltrating B cells, CD4+ T cells, neutrophils, and dendritic cells in BC. In conclusion, the findings of this study suggest that CDC20 may be involved in immunomodulating the tumor microenvironment and provide evidence that CDC20 inhibition may serve as a potential therapeutic approach for the treatment of BC patients. In addition, the data indicates that CDC20 can be a reliable prognostic biomarker for BC.

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