LncRNA HOTAIR up-regulation is strongly related with lymph nodes metastasis and LAR subtype of Triple Negative Breast Cancer

Abstract

Triple-negative breast cancers (TNBCs) represent a heterogeneous disease characterized by several molecular subtypes with different prognoses and responses to therapy. For a correct clinical management of TNBC patients the knowledge of the gene regulation mechanisms related to tumor progression and drug response has become fundamental. LncRNAs regulate gene expression through various processes, including chromatin modification, transcription and post-transcription and they are emerging as important cancer biomarkers being involved in tumor pathogenesis, metastatic progression and drug resistance. In this study we aimed to analyze the expression of the lncRNA HOTAIR, mainly involved in breast cancer disease, in a large case series of TNBC patients. We used ISH methods by a RNA probe to better define its staining in tumor tissues and its relation with clinical-pathological parameters and outcomes of patients. Our results show that high HOTAIR expression in tumor tissues is strongly correlated with lymph nodes metastasis (LNM) (p=0.039), as reported also for other tumor types, and has a direct strong association with Androgen Receptor (AR) expression (p= 0.019). These data confirm the prognostic role of HOTAIR in TNBC, and, its involvement in the regulation of AR pathway, suggests the possibility to establish new therapeutic strategies for AR+TNBC patients.

Keywords: Androgen Receptor; HOTAIR; TNBC.

Figure 1

Expression of HOTAIR in a series of TNBC samples: Expression levels were depicted as A) No staining or less than 1 dot to every 10 cells (Score 0) (60X magnification), B) average 2-3 dots/cell (Score 1) (60X magnification), C) average 4-6 dots/cell (Score 2) (60X magnification), and D) dot clusters >6 dots/cell (Score 3) (visible at 20-40X magnification). A staining detail is shown in the upper left square.

Figure 2

AR immunostaining in TNBC: A) Low expression of AR (20X); B) Low expression of AR (40X); C) High expression of AR (20X); D) High expression of AR (40X);

Figure 3

HOTAIR high expression TNBC patients Kaplan-Meier curves: A) Disease Free Survival (DFS) (pvalue=0.872 ); and B) Overall Survival (OS) (pvalue=0.990).