Abstract PS6-52: Identification of Aurora kinase A as a biomarker for prognosis in obesity patients with early breast cancer
Authors: Junnnan Xu, Tao Sun
Journal: Cancer Research (2021)

Abstract Background: Obesity is associated both with a higher risk of developing breast cancer, particularly in postmenopausal women, and with worse disease outcome for women of all ages. The molecular mechanisms that link obesity-breast cancer are complex and unclear. We hypothesized that overexpression of Aurora A was associated with poor survival in obesity breast cancer and related axis mechanism were involved.Methods: Fifty hundred and eighteen primary breast cancer specimens were collected from First Affiliated Hospital of China Medical University between January 2011 and November 2016. Our independent variable was BMI at baseline, categorized as overweight (BMI ≥ 25 kg/m2, as Obesity cohort), and normal (18.5 ≤ BMI &amp;lt; 25 kg/m2, as Non-obesity cohort). The Immunohistochemical (IHC) staining was performed with Aurora A, Survivin, MMP11, Cyclin B1 and Cathepsin L. Kaplan-Meier curve was used to analyze overall survival in our cohorts and TCGA-BRCA data (GSE3494). Log-rank test was used to calculate P value. PPI network analysis and MCODE model was used to analysis Aurora- altered signal pathway from GSE78958.Results: We validated Aurora A over expression using an independent cohort with a total of 517 breast carcinoma tissues (319 Non-Obesity patients and 198 Obesity Patients). The expression level of Aurora A-positive was significant higher in obesity breast carcinoma compared with non-obesity cancer carcinoma (χ2=9.79, P=0.002). In the immunohistochemistry assay, the results confirmed that the expression level of Aurora A-positive was significantly associated with hormone receptor status (68.4% vs 77.9%, P=0.015) and HER2 status (28.7% vs 17.9%, P=0.003). Aurora A-positive tumors had larger tumor size, though not statistically significant (78.1% vs. 71.1%, P=0.070). High Aurora A expression was remarkably and significantly associated with OS (8-year OS ratio: 69.5% vs 81.1%, OR=1.76, 95% CI:1.03~3.02, P=0.041) in Obesity Cohort. Interesting, higher expression of Aurora A was not associated with a shorter overall survival time among the Non-obesity breast cancer (8-year OS ratio:81.4% vs 85.8%, OR=1.40, 95% CI:0.79~2.45, P=0.229). As for RFS, the expression levels of Aurora A expression genes have no significance with RFS statistically in Non-Obesity patients. The in Aurora A low expression group was in high Aurora A expression in Non-Obesity Cohort ( 5-year RFS ratio:82.2% vs 83.2%, OR=1.29, 95% CI: 0.77~2.16, P=0.307). While 5-year RFS ratio in high Aurora A expression group of Aurora A were 71.3% was a little shorter than the 5-year RFS ratio in low Aurora A expression group (OR=1.58, 95% CI:0.96~2.57, P=0.072). Aurora A and Lymph node metastases were significantly poor prognostic factors for OS, and borderline significance was noted for high BMI. Kaplan-Meier survival analysis from TCGA database confirmed that the high Aurora A expression group had worse prognosis (HR=1.47, 95%CI:1.14-1.90, P=0.003). The KEGG pathway enrichment results were consistent with GO biological process term analysis, in which CCNB1 was enriched for upregulated Aurora A. In IHC correlation analyasis, Aurora A level on tumor cytoplasm had broad connections with Cyclin B1 (correlation coefficient = 0.227, P=0.001).Conclusions: Our finding demonstrate here for the first time that high expression of Aurora A was notably correlated with early recurrence and poor overall survival in obesity patients with early breast cancer. The Aurora A-Cyclin B1 axis could be a potential promising therapeutic target for cancer intervention and therapy. Keywords: Early breast cancer, obesity, Aurora A, Overall survival, Cyclin B1 Citation Format: Junnnan Xu, Tao Sun. Identification of Aurora kinase A as a biomarker for prognosis in obesity patients with early breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-52.