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Updated: Mar 27, 2026
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Identification and Validation of a Novel Theranostic Target in Triple Negative Breast Cancer with Transcriptomics and
Hyunjong Lee1,2, Giro Kim1,2, Mina Kim1
1Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Background:
Triple negative breast cancer (TNBC) poses a significant clinical challenge in imaging and therapy due to absence of conventional targets such as estrogen, progesterone, and HER2 receptors. The aim of this study is to identify potential targets for TNBC through comprehensive transcriptomic analyses and validation in TNBC cell lines and tissues.
Methods:
Single-cell RNA sequencing (scRNA-seq) data obtained from 8 TNBC patients and 11 normal patients were analyzed to identify differentially expressed surface proteins using adjusted p-values based on Bonferroni correction. To verify the validity of potential targets identified through scRNA-seq, expression of selected proteins was evaluated in bulk RNA-seq data from 162 TNBC and 113 normal breast tissues in the TCGA cohort. Finally, expression of selected proteins was examined in representative human TNBC cell lines and xenograft tumors in immunodeficient mice.
Results:
Nine proteins were revealed to be expressed more than twice as much in TNBC cells compared to normal cells: LY6E, LY6D, LAMP1, EMP2, TTYH1, CD74, BST2, HLA-DRA, and HLA-DRB1 (P < 10-10 for all). Among those, LY6E, LY6D, BST2, and TTYH1 were selected as potential target proteins with significantly higher expression in TNBC tissues (P < 0.0001 for LY6E and LY6D; P = 0.007 for BST2; P = 0.002 for TTYH1). Validation experiments revealed that LY6E demonstrated high expression on the membrane of TNBC cell lines, while exhibiting low expression in normal breast epithelial cells. Consistently, Western blot analysis of tumors from an in vivo xenograft model derived from a TNBC cell line confirmed elevated LY6E expression.
Conclusion:
In conclusion, this study suggests LY6E as a potential target for the selective imaging and therapy of TNBC, identified by transcriptomics analysis and cell line experiments. It lays the groundwork to augment clinical impact of future preclinical studies for the development of diagnostic and treatment approaches for TNBC.
Insights
Triple negative breast cancer (TNBC) lacks standard targets. This study identified LY6E as a promising new target for TNBC imaging and therapy through transcriptomic analysis and cell line validation.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Triple negative breast cancer (TNBC) presents significant challenges in diagnosis and treatment due to the absence of common molecular targets like estrogen, progesterone, and HER2 receptors.
- This necessitates the identification of novel therapeutic and diagnostic targets specific to TNBC.
Purpose of the Study:
- To identify and validate potential molecular targets for triple negative breast cancer (TNBC) through comprehensive transcriptomic analysis.
- To evaluate the expression of identified potential targets in TNBC cell lines and patient tissues for therapeutic and diagnostic applications.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) was employed to analyze gene expression in TNBC and normal breast tissues, identifying differentially expressed surface proteins.
- Potential targets were validated using bulk RNA-seq data from The Cancer Genome Atlas (TCGA) cohort and experimental evaluation in TNBC cell lines and xenograft models.
Main Results:
- Nine proteins showed significantly higher expression in TNBC compared to normal cells, including LY6E, LY6D, LAMP1, EMP2, TTYH1, CD74, BST2, HLA-DRA, and HLA-DRB1.
- LY6E, LY6D, BST2, and TTYH1 were confirmed as potential targets with significantly elevated expression in TNBC tissues.
- LY6E demonstrated high membrane expression in TNBC cell lines and elevated expression in xenograft tumor models, validating its potential as a target.
Conclusions:
- LY6E is proposed as a potential target for selective imaging and therapy of triple negative breast cancer.
- This research provides a foundation for future preclinical studies aimed at developing advanced diagnostic and therapeutic strategies for TNBC.
