Identification of ERBB Pathway-Activated Cells in Triple-Negative Breast Cancer.

Soo Young Cho

doi:10.5808/gi.2019.17.1.e3

Abstract

Intratumor heterogeneity within a single tumor mass is one of the hallmarks of malignancy and has been reported in various tumor types. The molecular characterization of intratumor heterogeneity in breast cancer is a significant challenge for effective treatment. Using single-cell RNA sequencing (RNA-seq) data from a public resource, an ERBB pathway activated triple-negative cell population was identified. The differential expression of three subtyping marker genes (ERBB2, ESR1, and PGR) was not changed in the bulk RNA-seq data, but the single-cell transcriptomes showed intratumor heterogeneity. This result shows that ERBB signaling is activated using an indirect route and that the molecular subtype is changed on a single-cell level. Our data propose a different view on breast cancer subtypes, clarifying much confusion in this field and contributing to precision medicine.

Highlights

Breast cancer is the most common cancer in women, and it is estimated that over 508,000 women have died due to breast cancer [1]
To identify functional differences in BC07 patient tumor cells, Gene Set Enrichment Analysis was performed, and the ERBB signaling pathway was enriched in a subpopulation of BC07 patient tumor cells
ERBB signaling was predominantly manifested by the ERBB2 gene in the human epidermal growth factor receptor 2 (HER2)+ subtype, not in TNBC

Summary

Introduction

Breast cancer is the most common cancer in women, and it is estimated that over 508,000 women have died due to breast cancer [1]. Five main intrinsic or molecular subtypes of breast cancer have been proposed: luminal A, luminal B, triple-negative (TNBC)/basal-like, human epidermal growth factor receptor 2 (HER2)-enriched (HER2+), and normal-like [2,3]. These breast cancer molecular subtypes have different gene expression patterns, clinical features, treatments, and prognoses. To understand intratumor heterogeneity expression patterns in breast cancer, a breast cancer cell population from single-cell RNA-seq (scRNA) data was analyzed from a public database. ERBB2 expression in a BC07 triple-negative patient was not significantly different in bulk-RNA and scRNA data. Our data propose a different view on breast cancer subtypes, clarifying much confusion in this field and contributing to precision medicine

Methods

Results

BC08 BC09

Discussion