Abstract P6-07-03: The prognostic impact of HECTD1 E3 ubiquitin ligase expression in breast cancer patients

Background: The epithelial-to-mesenchymal transition (EMT) is fundamental and is required for cancer cells to metastasize. A E3 ubiquitin ligase, HECTD1,wasidentified as a potent regulator of EMT in breast cancer patients. Depletion of HECTD1 was reported to enhance EMT and migration. Here, we investigated the correlation of HECTD1 mRNA expression with prognosis in early breast cancer patients during long-term follow-up. Materials and methods: A total of 627 invasive breast cancer tissues were analyzed for HECTD1 mRNA expression using a TaqMan PCR system. We also examined correlations between HECTD1 mRNA levels and clinicopathological factors in these samples. The median follow-up period was 10.2 years. Survival curves were analyzed using the Kaplan-Meier method. Cox proportional hazards regression analysis was used for univariate and multivariate analyses of prognostic values. Results: We identified positive correlations between low HECTD1 mRNA levels and shorter disease-free survival (DFS) and overall survival (OS) in breast cancer patients (P=0.02 and P=0.03, respectively). Low HECTD1 mRNA levels were positively correlated with high tumor grade, ERα and PgR negativity, HER2 positivity, and type of adjuvant therapy. Univariate analysis indicated that low HECTD1 mRNA levels was a factor for poor DFS and OS in breast cancer patients (hazard ratio (HR), 1.43; 95% confidence interval (CI), 1.06-1.95 and HR, 1.49; 95% CI, 1.03-2.17, respectively) (Table 1). Conclusion: We showed that low HECTD1 mRNA expression may be a predictive factor of poor prognosis in breast cancer patients. HECTD1 could therefore be a candidate biomarker and therapeutic target in breast cancer patients. Table 1. Univariate Cox regression analysis of HECTD1 mRNA expression associated with prognosis.Patients (n=617)UnivariateDisease-free survivalOverall survivalp valueHR (95%CI)p valueHR (95%CI)HectD1 mRNA expressionhigh3130.021(Reference)0.031(Reference)low3141.43(1.06-1.95)1.49(1.03-2.17) Citation Format: Yasuaki Uemoto, Naoto Kondo, Yumi Wanifuchi-Endo, Tomoko Asano, Tomoka Hisada, Sayaka Nishikawa, Yusuke Katagiri, Mitsuo Terada, Akiko Kato, Yu Dong, Hiroyuki Kato, Satoru Takahashi, Tatsuya Toyama. The prognostic impact of HECTD1 E3 ubiquitin ligase expression in breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-07-03.