Multiomics and single-cell sequencings reveal the specific biological characteristics of low Ki-67 triple-negative breast cancer

多组学和单细胞测序揭示低 Ki-67 三阴性乳腺癌的特定生物学特征

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作者:Boyue Han, Xiangchen Han, Hong Luo, Javaria Nasir, Chao Chen, Zhiming Shao, Hong Ling, Xin Hu

Background

Triple-negative breast cancer (TNBC) displays high heterogeneity. The majority of TNBC cases are characterized by high Ki-67 expression. TNBC with low Ki-67 expression accounts for only a small fraction of cases and has been relatively less studied.

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.

Methods

This study analyzed a large single-center multiomics TNBC data set, combined with a single-cell data set. The clinical, genomic, and metabolic characteristics of patients with low Ki-67 TNBC were analyzed.

Results

The clinical and pathological characteristics were analyzed in 2217 TNBC patients. Low Ki-67 TNBC was associated with a higher patient age at diagnosis, a lower proportion of invasive ductal carcinoma, increased alterations in the PI3K-AKT-mTOR pathway, upregulated lipid metabolism pathways, and enhanced infiltration of M2 macrophages. High Ki-67 TNBC exhibited a higher prevalence of TP53 gene 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.

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