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Updated: Aug 26, 2025
Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
Identification of tumor antigens and immune subtypes in breast cancer for mRNA vaccine development
Ruo Qi Li1,2, Wei Wang3, Lei Yan4
1Department of Pathology, Cancer Hospital Affiliated to Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China.
Background:
Poor prognosis, resistance to chemotherapy, insensitivity to radiotherapy, and a high prevalence of adverse drug reactions remain urgent issues for breast cancer (BC) patients. Increased knowledge of tumor immunobiology and vaccine development suggests the possibility of cancer vaccination. Here, we investigated potential BC-associated antigens for the development of an anti-BC mRNA vaccine and populations suitable for mRNA vaccination.
Methods:
Gene expression and clinical data were obtained from The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC). The single-cell sequencing data were obtained from the Single Cell Portal platform. cBioPortal was used to visualize and compare genetic alterations. Correlations between immune cell infiltration and antigen expression were visualized with the Tumor Immune Estimation Resource (TIMER). Immune subtypes were identified by consensus clustering and analysis of immune infiltration. Biomarkers for the assessment of mRNA vaccination suitability were investigated.
Results:
Three tumor-associated antigens, CD74, IRF1, and PSME2, that showed overexpression, amplification, and mutation and were linked with prognosis and immune cell infiltration, were identified. Single-cell sequencing analysis showed the expression of the three tumor-associated antigens in different cells of BC. Three immune subtypes were identified among BC patients, with Cluster B patients having a tumor microenvironment conducive to immunotherapy. These subtypes also showed different expression patterns of immune checkpoints, immune cell death-promoting genes, and response to immune checkpoint inhibitor (ICI) therapy. Thus, we identified five biomarkers that could be applied for assessing vaccination suitability and predicted drugs that would be appropriate for patients unsuited for vaccination.
Conclusions:
Our findings suggest new directions for the development of mRNA vaccines against breast cancer.
Insights
Researchers identified three breast cancer antigens (CD74, IRF1, PSME2) for mRNA vaccine development. They also found biomarkers to assess patient suitability for this novel breast cancer immunotherapy.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Breast cancer (BC) presents challenges including poor prognosis and treatment resistance.
- Advances in tumor immunobiology and cancer vaccines offer new therapeutic avenues.
- Investigating BC-associated antigens is crucial for developing effective mRNA vaccines.
Purpose of the Study:
- To identify potential breast cancer-associated antigens for mRNA vaccine development.
- To determine patient populations suitable for mRNA vaccination strategies.
- To explore biomarkers for assessing vaccination suitability in breast cancer.
Main Methods:
- Utilized gene expression and clinical data from TCGA and METABRIC databases.
- Analyzed single-cell sequencing data and visualized genetic alterations via cBioPortal.
- Correlated immune cell infiltration with antigen expression using TIMER and identified immune subtypes.
Main Results:
- Identified CD74, IRF1, and PSME2 as overexpressed, amplified, or mutated tumor-associated antigens linked to prognosis and immune infiltration.
- Single-cell analysis confirmed antigen expression in diverse BC cells.
- Discovered three immune subtypes, with Cluster B patients showing a favorable tumor microenvironment for immunotherapy and distinct responses to immune checkpoint inhibitors.
Conclusions:
- The study identifies novel targets and biomarkers for breast cancer mRNA vaccine development.
- Findings pave the way for personalized immunotherapy strategies in breast cancer patients.
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