Dissecting tumor antigens and immune subtypes for mRNA vaccine development in breast cancer

Abstract

Abstract Purposes Cancer mRNA vaccines are a promising strategy and a hot topic in cancer immunotherapy. However, mRNA vaccines for breast cancer (BRCA) remain undeveloped. This study aimed to identify potential tumor antigens for mRNA vaccine development and a population with BRCA suitable for vaccination. Methods Gene expression profiles and the clinical information of the TCGA-BRCA (the Cancer Genome Atlas Breast Cancer) and METABRIC (Molecular Taxonomy of Breast Cancer International Consortium) cohorts were downloaded from the TCGA and cBioPortal databases, respectively. cBioPortal was used to identify mutant genes. DEG (differentially expressed gene) identification and survival analysis were performed with the GEPIA2 tool. ssGSEA (single-sample gene set enrichment analysis) was applied to estimate abundances of 28 immune cells for each sample. An unsupervised consensus clustering algorithm was used to identify ISs (immune subtypes). A graph learning-based dimensionality reduction analysis algorithm was utilized to construct an immune landscape. WGCNA (weighted correlation network analysis) was performed to identify immune gene modules. Results Four potential tumor antigens, i.e., SLC7A5, CHPF, CCNE1, and CENPW, associated with poor prognosis and APCs (antigen-presenting cells) among overexpressed and mutated genes were identified in BRCA. Two ISs (IS1-2) characterized by distinct clinical, immune cell infiltration, and molecular features were observed in both the TCGA-BRCA and METABRIC cohorts. BRCA patients with IS2 tumors related to poor prognosis had an immune "hot" phenotype, while those patients with IS1 tumors related to superior prognosis had an immune "cold" phenotype. Distinct IS tumors were observed in different ICD (immunogenic cell death modulator) and ICP (immune checkpoint) expression profiles. The immune landscape showed an immune distribution in BRCA patients. Additionally, we identified 2 immune gene modules with different biological functions. Conclusions SLC7A5, CHPF, CCNE1, and CENPW are the potential tumor antigens for mRNA vaccine development with BRCA. Patients with IS2 tumors are a suitable population for mRNA vaccination. This study provides a new insight into mRNA vaccine development, population selection for vaccination, and prognosis prediction.

Keywords

• Breast cancer
• mRNA vaccine
• Immune subtypes
• Tumor antigens
• Immune landscape
• Immune gene module