Abstract P1-05-09: Role of long non coding RNAs in response to neoadjuvant therapy in triple negative and Her2+ subtypes breast cancer
Authors: Salvador Javier , Gil Ana , Benavent Marta , Molina-Pinelo Sonia , Gonzalez Rosario , Montaño Álvaro , Ruiz Manuel , Falcón Alejandro , Sánchez Alberto , Garrigós Carmen 
Published: March 2020

Background: Long non-coding RNAs (LncRNAs) are important regulators of gene expression, acting at almost all regulatory levels, both transcriptional and post-transcriptional. It has been described that LncRNAs have a relevant role both in biological processes and in the growth and progression of tumors. Specifically, LncRNAs have been identified in breast cancer as predictors in the development of the disease. Nowadays, neoadjuvant systemic therapy for breast cancer is used increasingly but, there is a group of patients which do not benefit from this therapy. With these premises, we stablished that our main objective was to identify the differential expression LncRNAs in paraffin-embedded breast cancer samples ER-PR-/Her2+, ER+PR+/Her2+ and triple negative (TN) subtypes in responders (R) and non-responders (NR) patients (pts) to neoadjuvant therapy.

Methods: All samples were collected from biobank of University Hospital Virgen del Rocio. RNA from formalin fixed paraffin embedded tumor samples from 40 pts with breast cancer that had received neoadjuvant therapy was extracted with mirVana miRNA isolation kit (Ambion). All samples were diagnostic biopsies. Patients with TN subtype received neoadjuvant chemotherapy based on anthracyclines and taxanes and patients with the Her2+ subtype received treatment with taxanos-trastuzumab and anthracyclines. The expression RNAs was analyzed by ClariomD Asssay (ThermoFisher). Results were analyzed with Transcriptome Analysis Console and with in-house scripts in R (version 3.5.1). Data were corrected and normalized using Robust Multichip Average method from the oligo package. Expression was summarized at gene level using the corresponding annotation for ClariomD array BrainArray. Expression analyses were performed with limma package. A fold change ≥ 2 and p&lt;0.05 was considered statistically significant. We defined to groups: R (response, RCB 0) and NR (not response, RCB III) pts.

Results: From the analysis of the results, we obtained seventeen LncRNAs differentially expressed in R vs NR groups. The expression of these LncRNAs was also different in each subtype of patients. A fold change ≥ 2, p&lt;0.05 and p adj&lt;0.05 was considered. Respect to TN, four LncRNAs (LINC01282, RP11-280G9.1, AC079988.3 and RP11-645C24.5) were differentially expressed between R (n=11) and NR (n=6). In ER-PR-/Her2+ subgroup, eight LncRNAs (RP1-290I10.5, RP11-140I16.3, RP1-288H2.2, RP4-704D23.1, LINC01087, WASIR2, CTD-3025N20.3, RP11-227G15.11) showed a differential expression in R (n=10) vs NR (n=3). Patients with ER+PR+/Her2+ (RP11-138I1.3, LINC01243, MIR2052HG, RP11-245A18.1, AC091814.2) showed five differentially expressed in R (n=8) vs NR (n=2). (See Table 1).

Conclusions: We found seventeen LncRNAs differentially expressed in the different molecular cancer subtypes involved in the response to neoadjuvant therapy. In particular, RP1-290I10.5, RP11-140I16.3, RP1-288H2.2, RP4-704D23.1, LINC01087 in ER-PR-/Her2+ subtype showed a strong difference with a significant adjusted p-value and a fold change more than 2. These results suggest that these LncRNAs could represent valid predictive biomarkers in neoadjuvant therapy for these patients.

Table 1p adj &lt; 0.05FC &gt; 2p &lt;0.05TNLINC01282AC079988.3AC079988.3RP11-280G9.1RP11-645C24.5RP11-645C24.5ER-PR-/Her2+RP1-290i10.5RP1-290i10.5RP11-140I16.3RP11-140I16.3RP1-288H2.2RP1-288H2.2RP4-704D23.1RP4-704D23.1LINC01087LINC01087WASIR2WASIR2CTD-3025N20.3CTD-3025N20.3RP11-227G15.11RP11-227G15.11ER+PR+/Her2+RP11-138I1.3LINC01243MIR2052HGRP11-245A18.1AC091814.2

Citation Format: Javier Salvador, Ana Gil, Marta Benavent, Sonia Molina-Pinelo, Rosario Gonzalez, Álvaro Montaño, Manuel Ruiz, Alejandro Falcón, Alberto Sánchez, Carmen Garrigós. Role of long non coding RNAs in response to neoadjuvant therapy in triple negative and Her2+ subtypes breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-05-09.