Abstract P4-07-04: Immunohistochemical determination of arylamine N-acetyltransferase 1 (NAT1) as the target of miR-1290 and prognostic biomarker of breast cancer

Abstract

Abstract Introduction: There are large-scale molecular differences between estrogen receptor α (ERα)-positive breast cancer and ER-negative breast cancers. In ERα-positive breast cancer, recent analyses have shown that ERα-positives can be divided into two subtypes such as luminal A and luminal B. These subtypes differ in characteristics such as response to endocrine therapy and chemotherapy, and prognosis. In a previous study, we identified a microRNA, miR-1290, that was significantly down-regulated in luminal A tumors and its potential target arylamine N-acetyltransferase 1 (NAT1). The aim of this study was to clarify whether NAT1 is a bona fide target of miR-1290, and to investigate the impact of NAT1 on breast cancer prognosis. Methods: Luciferase reporter assay was employed to validate NAT1 as a putative miR-1290 target gene. Protein expressions of NAT1, ERα, progesterone receptor (PgR) and HER2 were analyzed in 394 breast cancer samples by immunohistochemistry. Results: NAT1 was shown to be a direct target of miR-1290 by luciferase reporter assay. Expression levels of NAT1 were positively correlated with expression levels of ERα (P < 0.0001) and PgR (P < 0.0001), whereas expression levels of NAT1 were negatively correlated with both tumor grade and tumor size (P < 0.0001). Kaplan-Meier analysis showed that NAT1 presence was significantly associated with increased overall survival (OS) (P = 0.0416) in breast cancer patients (n=394). Similarly, significant associations of NAT1 presence were shown with disease-free survival (DFS) (P = 0.0048) and OS (P = 0.0055) in patients who received adjuvant endocrine therapy with tamoxifen (n = 176). Moreover, NAT1 presence was also significantly associated with increased DFS (P = 0.0025) and OS (P = 0.0007) in lymph node-positive breast cancer patients (n=147). Univariate and multivariate analyses showed significant associations between expression levels of NAT1 and DFS (P = 0.0005 and 0.019, respectively). Conclusion: We reported that miR-1290 directly targets NAT1 3’-UTR and NAT1 protein expression is correlated with improved OS of breast cancer. Moreover, NAT1 is a possible prognostic biomarker for lymph node-positive breast cancer. Thus, miR-1290 and its potential target NAT1 are associated with characteristics of breast cancer. Citation Format: Yumi Endo, Hiroko Yamashita, Satoru Takahashi, Shinya Sato, Nobuyasu Yoshimoto, Tomoko Asano, Yukari Hato, Mina Yamaguchi, Yu Dong, Tatsuya Toyama. Immunohistochemical determination of arylamine N-acetyltransferase 1 (NAT1) as the target of miR-1290 and prognostic biomarker of breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-07-04.