Development of a CD8+ T cell-based molecular classification for predicting prognosis and heterogeneity in triple-negative breast cancer by integrated analysis of single-cell and bulk RNA-sequencing

Yin-Wei Dai; Wei-Ming Wang; Xiang Zhou

doi:10.1016/j.heliyon.2023.e19798

Development of a CD8⁺ T cell-based molecular classification for predicting prognosis and heterogeneity in triple-negative breast cancer by integrated analysis of single-cell and bulk RNA-sequencing

Heliyon. 2023 Sep 6;9(9):e19798. doi: 10.1016/j.heliyon.2023.e19798. eCollection 2023 Sep.

Authors

Yin-Wei Dai¹, Wei-Ming Wang², Xiang Zhou¹

Affiliations

¹ Department of Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, China.
² Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Abstract

Background: Triple-negative breast cancer (TNBC), although the most intractable subtype, is characterized by abundant immunogenicity, which enhances responsiveness to immunotherapeutic measures.

Methods: First, we identified CD8⁺ T cell core genes (TRCG) based on single-cell sequence and traditional transcriptome sequencing and then used this data to develop a first-of-its-kind classification system based on CD8⁺ T cells in patients with TNBC. Next, TRCG-related patterns were systematically analyzed, and their correlation with genomic features, immune activity (microenvironment associated with immune infiltration), and clinicopathological characteristics were assessed in the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), the Cancer Genome Atlas (TCGA), GSE103091, GSE96058 databases. Additionally, a CD8⁺ T cell-related prognostic signature (TRPS) was developed to quantify a patient-specific TRCG pattern. What's more, the genes-related TRPS was validated by polymerase chain reaction (PCR) experiment.

Results: This study, for the first time, distinguished two subsets in patients with TNBC based on the TRCG. The immune microenvironment and prognostic stratification between these have distinct heterogeneity. Furthermore, this study constructed a novel scoring system named TRPS, which we show to be a robust prognostic marker for TNBC that is related to the intensity of immune infiltration and immunotherapy. Moreover, the levels of genes related the TRPS were validated by quantitative Real-Time PCR.

Conclusions: Consequently, this study unraveled an association between the TRCG and the tumor microenvironment in TNBC. TRPS model represents an effective tool for survival prediction and treatment guidance in TNBC that can also help identify individual variations in TME and stratify patients who are sensitive to anticancer immunotherapy.

Keywords: CD8+ T cell; Heterogeneity; Triple-negative breast cancer; Tumor immune microenvironment; single cell sequencing.