Abstract
MicroRNA-454 (miR-454) has been reported to play an oncogenic or tumor suppressor role in most cancers. However, the clinical relevance of miR-454 in breast cancer remains unclear. We examined the expression of miR-454 in a tissue microarray containing 534 breast cancer specimens from female patients at Fudan University Shanghai Cancer Center using in situ hybridization (ISH). Of these, 250 patients formed the training set and the other 284 were the validation set. The relationship between miR-454 and clinical outcome was analyzed by the Kaplan-Meier method. High expression of miR-454 indicated worse disease-free survival (DFS) in both cohorts (P = 0.006 for training set; P = 0.010 for validation set). Furthermore, in the triple-negative breast cancer (TNBC) subtype, miR-454 was positively correlated with worse clinical outcome (P = 0.013 for training set, P = 0.014 for validation set). In addition, patients in the low miR-454 expression cohort had better response to anthracycline compared to non-anthracycline chemotherapy (P = 0.056), but this difference was not observed in the high miR-454 expression cohort. Our findings indicated that miR-454 is a potential predictor of prognosis and chemotherapy response in TNBC.
Highlights
Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females worldwide, with an estimated 1.7 million cases and 521,900 deaths in 2012 [1]
Www.impactjournals.com/oncotarget miRNAs have been reported to regulate a variety of cellular processes, including tumor progression and metastasis, implying that they might function as biomarkers for diagnosis, prognosis, and therapy response in cancers [19,20,21,22]
MiR-454 appeared to function as an oncogene or a tumor suppressor because its expression correlated negatively or positively with tumor biological characteristics and clinical outcome
Summary
Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females worldwide, with an estimated 1.7 million cases and 521,900 deaths in 2012 [1]. Triplenegative breast cancers are defined as tumors that lack expression of estrogen receptor (ER), progesterone receptor (PR), and HER2, and patients with triple-negative tumors have a relatively poor outcome [3]. Because of their specific receptor status, patients with triple-negative breast cancer do not benefit from endocrine therapy or trastuzumab [4]. Numerous studies have shown that miR454 expression correlates with tumor growth, invasion, and metastasis in many cancers; miR-454 has a dual function, and can act as an oncogenic miRNA or a tumor suppressor. In Hispanic women, miR-454 was overexpressed in the group of women diagnosed with breast cancer < 5.2 years postpartum compared with the late diagnosis group [14]
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