Abstract

Luminal breast cancers (BC) account for majority of breast cancer. Due to its heterogeneity and the development of treatment resistance, luminal BC patients can vary substantially. Long noncoding RNAs (lncRNAs), as we known, is involved in breast cancer progression. Here, we aim to identify the lncRNAs which are involved in the particular type luminal BC progression. By Gene Chips analysis, we found a novel lncRNA00544, which was highly expressed in the metastatic axillary nodes compared with corresponding luminal BC tissues (fold change = 2.26, P = 0.043). This result was confirmed in luminal BC cell lines (p = 0.0113) and 49 paired breast cancer samples compared with in corresponding controls (p = 0.011). Furthermore, Kaplan–Meier survival curves of 373 breast cancer patients indicated that disease-free survival was significantly poor in breast cancer patients with high lncRNA00544 expression (p < 0.001). Univariate and multivariate Cox regression analyses showed that lncRNA00544 was a significant independent prognostic biomarker in luminal BC patients. Further analysis showed that the prognosis of high lncRNA00544 expression in breast cancer patients was actually related to HR + HER2− subtype. Together, our studies indicate that lncRNA00544 may represent a novel predictive and prognostic indicator in luminal BC patients.

Highlights

  • Breast cancer (BC) is the most common cancer of women worldwide, and approximately 60–75% of cases are luminal tumors[1,2]

  • To confirm the differential expression of lncRNA00544 in breast cancer, we showed that the expression of lncRNA00544 was increased in all breast cancers (BC) cell lines compared with a normal breast cell line (MCF10A) (p < 0.05, Fig. 1A)

  • The relative expression of lncRNA00544 was further analyzed in 49 paired breast cancer tissues and matched metastatic axillary nodes by quantitative real-time polymerase chain reaction (qRT-PCR) normalized to GAPDH

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Summary

Introduction

Breast cancer (BC) is the most common cancer of women worldwide, and approximately 60–75% of cases are luminal tumors[1,2]. Overexpression of metastasis associated in lung adenocarcinoma transcript 1 (MALAT1) is associated with poor prognosis in tamoxifen-treated ER+ breast cancer patients, and might be considered as a potential biomarker to predict endocrine treatment sensitivity[25] These previous reports focused on ER+ breast cancer. Based on the results of the array analysis, we focused on a novel lncRNA00544 (ENST00000544591, 4687 nucleotides; chromosome 12 (+): 10705962–10710648), which was highly expressed in metastatic axillary nodes compared with BC tissue samples To determine whether this novel lncRNA might be a potential biomarker for the progression of luminal BC, the expression of lnc00544 in breast cancer tissues and axillary nodes was compared by quantitative real-time polymerase chain reaction (qRT-PCR). The predictive value of lnc00544 expression for prognosis in HR+/ HER2− breast cancer was evaluated by Kaplan-Meier and Cox regression analysis

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