LncRNAs as new biomarkers to differentiate triple negative breast cancer from non-triple negative breast cancer.

Mingming Lv,Rong Shen,Xuemei Jia,Ying Wu,Hui Xie,Yun Gu,Ziyi Fu,Hongyan Yuan,Xin Zeng,Pengfei Xu,Xiaowei Wu,Yongmei Yin,Shanshan Lv,Wenqu Li,Lei Huang

doi:10.18632/oncotarget.7509

Abstract

Triple negative breast cancer (TNBC) is an aggressive type of breast cancer with high heterogeneity. To date, there is no efficient therapy for TNBC patients and the prognosis is poor. It is urgent to find new biomarkers for the diagnosis of TNBC or efficient therapy targets. As an area of focus in the post-genome period, long non-coding RNAs (lncRNAs) have been found to play critical roles in many cancers, including TNBC. However, there is little information on differentially expressed lncRNAs between TNBC and non-TNBC. We detected the expression levels of lncRNAs in TNBC and non-TNBC tissues separately. Then we analyzed the lncRNA expression signature of TNBC relative to non-TNBC, and found dysregulated lncRNAs participated in important biological processes though Gene Ontology and Pathway analysis. Finally, we validated these lncRNA expression levels in breast cancer tissues and cells, and then confirmed that 4 lncRNAs (RP11-434D9.1, LINC00052, BC016831, and IGKV) were correlated with TNBC occurrence through receiver operating characteristic curve analysis. This study offers helpful information to understand the initiation and development mechanisms of TNBC comprehensively and suggests potential biomarkers for diagnosis or therapy targets for clinical treatment.

Highlights

Breast cancer is the leading cause of cancer mortality among women worldwide
Considering the high heterogeneity of Triple negative breast cancer (TNBC), it is difficult to confirm which subsets of TNBC patients are likely to respond to specific chemotherapeutics, and there are no reliable biomarkers that could be used as a screening marker
The results showed that the receiver operating characteristic (ROC) curve for RP11-434D9.1 had an area under the curve (AUC) of 0.792; the LINC00052 AUC was 0.823; the IGKV AUC was 0.854; the BC016831 AUC was 0.802; the CTC-338M12.3 AUC was 0.917; the C17orf76-AS1 AUC was 0.927; the RP4-781K5.4 AUC was 0.54; and the LOC441242 AUC was 0.667

Summary

Introduction

Breast cancer is the leading cause of cancer mortality among women worldwide. The incidence of breast cancer has been increasing by 3% per year in China, which has threatened the health of women and created a great burden on society [1]. Based on gene expression profiling, breast cancer has been categorized into four major subtypes: luminal A, luminal B, human epidermal growth factor receptor 2 positive (Her. 2 +), and basal-like [2]. 2 +), and basal-like [2] According to these categories, developments in clinical treatment strategy, including the foundation of endocrine therapy and Her-2 targeted therapy, have improved the survival levels of breast cancer patients. Triple negative-breast cancer (TNBC), which is characterized by the lack of an estrogen receptor (ER), progesterone receptor (PR), and Her-2 overexpression, could not benefit from both endocrine therapy and Her-2 targeted therapy [3]. Chemotherapy is the unique systemic treatment for TNBC, patients with TNBC probably have a worse treatment response and poorer outcomes after chemotherapy compared with www.impactjournals.com/oncotarget the patients with breast cancers of other subtypes [4, 5]. It is urgent to identify novel biomarkers and potential therapeutic targets for this aggressive TNBC phenotype

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