Multi-Omics and Single-Cell Sequencing Reveal the Genomic Features and Metabolic Heterogeneity of Low Ki-67 Triple-Negative Breast Cancer

Abstract Background: TNBC displays high heterogeneity and the majority of TNBC cases were characterized by a high Ki-67 expression. In contrast, TNBC with low Ki-67 expression accounts for only a small fraction, and this subset of TNBC has been relatively less extensively studied. Methods: Using the study institution's largest single-center multi-omics TNBC dataset combined with a single-cell dataset, the authors analyzed the clinical, genomic, and metabolic characteristics of patients with low Ki-67 TNBC. Results: This study included a total of 2217 low Ki-67 TNBC patients for the analysis of clinical and pathological characteristics. The results revealed that patients with low Ki-67 TNBC had a higher age at diagnosis, a lower proportion of invasive ductal carcinoma (IDC), increased alterations in the PI3K-AKT-mTOR pathway, upregulated lipid metabolism pathways, and enhanced infiltration of M2 macrophages. In contrast, high Ki-67 TNBC patients exhibited a higher prevalence of TP53 mutations, elevated nucleotide metabolism, and increased infiltration of M1 macrophages. Conclusions: We identified specific genomic and metabolic characteristics unique to low Ki-67 TNBC, which have implications for the development of precision therapies and patient stratification strategies.