Prognosis Prediction Through an Integrated Analysis of Single-Cell and Bulk RNA-Sequencing Data in Triple-Negative Breast Cancer.

Abstract

Background: Genomic and antigenic heterogeneity pose challenges in the precise assessment of outcomes of triple-negative breast cancer (TNBC) patients. Thus, this study was designed to investigate the cardinal genes related to cell differentiation and tumor malignant grade to advance the prognosis prediction in TNBC patients through an integrated analysis of single-cell and bulk RNA-sequencing (RNA-seq) data. Methods: We collected RNA-seq and microarray data of TNBC from two public datasets. Using single-cell pseudotime analysis, differentially expressed genes (DEGs) among trajectories from 1534 cells of 6 TNBC patients were identified as the potential genes crucial for cell differentiation. Furthermore, the grade- and tumor mutational burden (TMB)-related DEGs were explored via a weighted correlation network analysis using the Molecular Taxonomy of Breast Cancer International Consortium dataset. Subsequently, we utilized the DEGs to construct a prognostic signature, which was validated using another independent dataset. Moreover, as gene set variation analysis indicated the differences in immune-related pathways between different risk groups, we explored the immune differences between the two groups. Results: A signature including 10 genes related to grade and TMB was developed to assess the outcomes of TNBC patients, and its prognostic efficacy was prominent in two cohorts. The low-risk group generally harbored lower immune infiltration compared to the high-risk group. Conclusion: Cell differentiation and grade- and TMB-related DEGs were identified using single-cell and bulk RNA-seq data. A 10-gene signature for prognosis prediction in TNBC patients was constructed, and its performance was excellent. Interestingly, the signature was found to be closely related to tumor immune infiltration, which might provide evidence for the crucial roles of immune cells in malignant initiation and progression in TNBC.