Nrdp1 expression to predict clinical outcome and efficacy of adjuvant anthracyclines-based chemotherapy in breast cancer: A retrospective study

Article type: Research Article

Authors: Jiao, Shiping^{a; b; d} | Liu, Wenjie^{a; b; d} | Wu, Minqing^{a; c} | Peng, Cheng^{a; b; d} | Tang, Hailin^{a; b} | Xie, Xiaoming^{a; b; *}

Affiliations: [a] Department of Breast Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China | [b] Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China | [c] Department of Cancer Prevention Center, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China | [d] Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China

Correspondence: [*] Corresponding author: Xiaoming Xie, Department of Breast Oncology, Sun Yat-Sen University Cancer Center, 651 E Dongfeng Rd, Guangzhou 510060, Guangdong, China. Tel.: +86 20 87343806; Fax: +86 20 87343805; E-mail: [email protected].

Abstract: Background:Existing reports showed loss of Nrdp1, an E3 ubiquitin ligase, promoted breast cancer malignancy because of failure to deregulate ErbB3. However, the correlation between Nrdp1 expression with clinical data is still unknown. Objective:We explored the predictive value of Nrdp1 regarding the clinical outcome of patients and the benefit of adjuvant anthracycline-based chemotherapy. Methods:113 primary breast cancer samples were obtained during surgery and the patients received average 10-year follow-up. We obtained Nrdp1 and ErbB3 expressions by immunohistochemstry. Results:Nrdp1 expression correlates with overall survival and disease-free survival of patients, with a hazard ratio of 0.237 (p=0.001) and 0.280 (p< 0.001) respectively. Additionally Nrdp1 correlates inversely with ErbB3 expression in tumor tissue (p=0.009). However the prognosis of Nrdp1 was not solely dependent on its regulation of ErbB3 degradation since there was also a significant correlation between Nrdp1 and overall survival (p=0.005) in ErbB3-negative patients. In patients who received anthracycline-based chemotherapy, low Nrdp1 expression indicated decreased disease-free survival (p=0.006) and high rates of metastasis and/or recurrence (p<0.001). Conclusion:Nrdp1 may serve as a useful biomarker for the clinical outcome and efficacy of adjuvant anthracyclines-based chemotherapy in breast cancer.The prognosis of Nrdp1 was not solely dependent on its deregulation of ErbB3.

Keywords: Nrdp1, ErbB3, breast cancer, biomarker, prognosis, anthracyclines-based chemotherapy

DOI: 10.3233/CBM-140443

Journal: Cancer Biomarkers, vol. 15, no. 2, pp. 115-123, 2015