Downregulation of CDC14B in 5218 breast cancer patients: A novel prognosticator for triple-negative breast cancer

Abstract

Breast cancer is the most common female malignancy worldwide and the prognosis of triple-negative breast cancer (TNBC) and advanced breast cancer patients is unsatisfying. The exploration of novel prognostic indicators and appropriate targets is crucial for improving the treatment outcomes of breast cancer patients. The cell division cycle protein 14B (CDC14B) is known for its roles in cell cycle control, but its expression status and molecular function in breast cancer is unknown. This study explores the expression patterns and clinical values of CDC14B in breast cancer tissues. For this research, the authors downloaded gene microarrays and RNA sequencing datasets to examine the expression levels of CDC14B in 5218 breast cancer tissues, comparing them to the expression levels in 1176 normal breast tissues. The relationships between CDC14B and clinicopathologic characteristics of breast cancer were also addressed. The mutation conditions of CDC14B were then clarified using cBioPortal. Finally, differentially expressed genes and co-expressed genes related to CDC14B were filtered using the Limma-Voom package. These genes were intersected to conduct functional annotations and to construct a protein-protein interaction network. It was observed that CDC14B was significantly downregulated in breast cancer tissues but not in normal breast tissues (standardized mean difference= −1.17 [−1.50-−0.85], area under the curve = 0.88). In addition, CDC14B downregulation was correlated with the poor prognosis of TNBC patients (hazard ratios < 1; p < 0.05). Amplification was detected to be the most frequent alteration of CDC14B. The presence of this alteration forecasted unfavourable overall survival outcomes in breast cancer patients (p < 0.05). Dysregulated genes that co-expressed with CDC14B were pivotal in cell cycle (namely mitotic-nuclear division and DNA packaging complex) and cancer-related signaling pathways (namely the peroxisome proliferators activated receptor [PPAR] signalling pathway and the AMP-activated protein kinase [AMPK] signalling pathway). Moreover, the genes ADIPOQ and CCNE2 were identified as two promising prognostic factors in breast cancer. In summary, CDC14B was downregulated in breast cancer tissue and may be a promising hallmark in TNBC patients. The dysregulated genes co-expressed with CDC14B may play an important role in the development of breast cancer through PPAR and AMPK signalling pathways.