Biomarkers involved in the neoadjuvant therapy response in triple-negative and Her2+ subtypes breast cancer.

Abstract

e12098 Background: Neoadjuvant systemic therapy for breast cancer is used increasingly for patients with breast cancer. One of the more compelling theoretical arguments for primary systemic therapy is its value as an in vivo test for drug sensitivity. The oncogenesis of breast cancer, progression and development of metastasis is influenced by the deregulation of a multitude of processes. Several long non-coding RNAs (LncRNAs) and genes are important regulators of gene expression, acting at almost all regulatory levels: transcriptional, posttranscriptional, epigenetic, and protein translation. Our main objective was to identify the differential expression of genes and LncRNAs in paraffin-embedded breast cancer samples Her2+ and triple negative (TN) subtypes in responders (R) and non-responders (NR) patients (pts) to neoadjuvant therapy. Methods: 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. We defined R (RCB 0; n = 29) and NR (RCB III; n = 11) pts. Results: The differential expression (p < 0.01) of two LncRNAs (RP1-213J1P_B.1 and AC053503.12), one miscellaneous RNA (miscRNA) (Metazoa_SRP) and five genes (STMND1, C8orf33, RP11-144G6.12, ZNF555, RGS2) were found between R and NR. Among others, we highlighted one of these LncRNAs (AC053503.12) and one gene (Metazoa_SRP) that were also identified in TN R (n = 11) vs NR (n = 6). In the Her2+subtype, STMND1 gene also showed a differential expression in R (n = 18) vs NR (n = 5). Conclusions: We found these LncRNAs, miscRNA and genes were involved in different cancer pathways and the their differential expression in R vs NR pts suggest that they could be involved in the response to neoadjuvant therapy in TN and Her2+ subtypes breast cancer. LncRNAs, miscRNA and genes differentially expressed are being independently analyzed by individual qPCR assays in the study cohort.