Single-cell RNA-seq dissects the intratumoral heterogeneity of triple-negative breast cancer based on gene regulatory networks

• Published in: Molecular therapy. Nucleic acids Vol. 23; pp. 682 - 690
• Main Authors: Zhou, Shunheng, Huang, Yu-e, Liu, Haizhou, Zhou, Xu, Yuan, Mengqin, Hou, Fei, Wang, Lihong, Jiang, Wei
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05.03.2021; American Society of Gene & Cell Therapy; Elsevier
• Subjects: cell-cell communication; gene regulatory network; intratumoral heterogeneity; key regulator; Original; single-cell RNA sequencing; triple-negative breast cancer; tumor microenvironment; single-cell RNA sequencing; triple-negative breast cancer; intratumoral heterogeneity; key regulator; tumor microenvironment; cell-cell communication; gene regulatory network
• ISSN: 2162-2531; 2162-2531
• DOI: 10.1016/j.omtn.2020.12.018

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with high intratumoral heterogeneity. Recent studies revealed that TNBC patients might comprise cells with distinct molecular subtypes. In addition, gene regulatory networks (GRNs) constructed based on single-cell RNA sequencing (scRNA-seq) data have demonstrated the significance for decoding the key regulators. We performed a comprehensive analysis of the GRNs for the intrinsic subtypes of TNBC patients using scRNA-seq. The copy number variations (CNVs) were inferred from scRNA-seq data and identified 545 malignant cells. The subtypes of the malignant cells were assigned based on the PAM50 model. The cell-cell communication analysis revealed that the macrophage plays a dominant role in the tumor microenvironment. Next, the GRN for each subtype was constructed through integrating gene co-expression and enrichment of transcription-binding motifs. Then, we identified the critical genes based on the centrality metrics of genes. Importantly, the critical gene ETV6 was ubiquitously upregulated in all subtypes, but it exerted diverse roles in each subtype through regulating different target genes. In conclusion, the construction of GRNs based on scRNA-seq data could help us to dissect the intratumoral heterogeneity and identify the critical genes of TNBC. [Display omitted] Jiang and colleagues performed a comprehensive analysis of the GRNs for the intrinsic subtypes of TNBC patients using scRNA-seq. The cell-cell communication analysis revealed that the macrophage plays a dominant role in the tumor microenvironment. In addition, the critical gene ETV6 exerted diverse roles in each subtype through regulating different target genes.