Abstract
Background:Aurora kinase A (AURKA) is considered one of the key players in cancer biology, and it has been the subject of intense investigation. It plays a critical role in activating PLK1 by phosphorylating the Thr210 site within the T-loop of its kinase domain.AURKA phosphorylates Cyclin B1, which significantly enhances its stability and functional activity. FOXM1 recruits nuclear AURKA to promote the self-renewal of breast cancer stem cells, while AURKA stabilizes FOXM1 to boost the proliferation of breast cancer cells. AURKA modulates β-catenin within the Wnt signaling pathway by phosphorylating its Ser552 and Ser675 sites and sustaining oncogenic signaling. AURKA triggers the NF-κB pathway, a mechanism closely tied to tumor progression and apoptosis resistance.Ultimately, the activation of AURKA drives the upregulation of MMP-9 through both β-catenin and NF-κB signaling, markedly increasing the invasive potential of cancer cells.
Objective:To investigate the association between AURKA activity and molecules involved in cell-cycle regulation, oncogenic signaling, and cancer progression in the Iraqi women population.
Methods:A case-control study was carried out on 50 newly diagnosed BC patients (based on histopathological examination from a core needle biopsy) and 40 healthy controls (underwent a regular breast screening using mammography or ultrasonic examination) of matched age and BMI admitted to Al-Elwiya Teaching Hospital for the Maternity/Breast Cancer Early Detection Center. Blood samples were collected to evaluate the levels of Aurora A, Plk1, Cyclin B1, FOXM1, β-catenin, NF-κB, and MMP-9 using ELISA kits. Statistical analysis was performed with SPSS.
Results:Serum concentrations of AURKA, Plk1, Cyclin B1, β-catenin, and MMP-9 were significantly elevated in BC cases compared with controls, with median values of 3.67 (IQR: 3.49–3.90 ng/mL) and 2.79 (IQR: 2.54–3.37 ng/mL), 110.95 (IQR: 96.94–123.37 pg/mL) versus 73.18 (IQR: 68.35–81.70 pg/mL), 4.63 (IQR: 4.24–5.08 ng/mL) and 3.49 (IQR: 3.24–3.71 ng/mL), and 2.73 (IQR: 2.58–2.87 ng/mL) compared with 1.95 (IQR: 1.75–2.17 ng/mL) and 4.67 (IQR: 4.15–5.48 ng/mL) compared with 2.58 (IQR: 2.15–2.92 ng/mL), respectively (P < 0.001). For FOXM1 and NF-κB, mean serum concentration was significantly higher in BC cases (286.10 ± 54.24 pg/mL) than controls (158.59 ± 23.85 pg/mL) and (2.96 ± 0.49 ng/mL) versus (5.64 ± 0.92 ng/mL), respectively (P < 0.001).
Conclusions: Our findings indicate higher Aurora-A related biomarkers levels in BC women associated with higher tumor cell proliferation, migration, invasion, and metastasis.
