Combined Single‐Cell and Spatial Transcriptomics Reveal the Metabolic Evolvement of Breast Cancer during Early Dissemination

• Published in: Advanced science Vol. 10; no. 6; pp. e2205395 - n/a
• Main Authors: Liu, Yi‐Ming, Ge, Jing‐Yu, Chen, Yu‐Fei, Liu, Tong, Chen, Lie, Liu, Cui‐Cui, Ma, Ding, Chen, Yi‐Yu, Cai, Yu‐Wen, Xu, Ying‐Ying, Shao, Zhi‐Ming, Yu, Ke‐Da
• Format: Journal Article
• Language: English
• Published: Germany John Wiley & Sons, Inc 01.02.2023; John Wiley and Sons Inc; Wiley
• Subjects: Breast cancer; Breast Neoplasms - metabolism; Cells; early dissemination; Female; Gene expression; Genomics; Glycolysis - genetics; Humans; Lymph Nodes; Lymphatic Metastasis - genetics; Lymphatic Metastasis - pathology; Lymphatic system; Medical research; Metabolism; Metastasis; Phosphorylation; single‐cell RNA sequencing; spatial transcriptomics; Transcriptome - genetics; Tumors; single-cell RNA sequencing; breast cancer; metabolism; early dissemination; spatial transcriptomics
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202205395

Breast cancer is now the most frequently diagnosed malignancy, and metastasis remains the leading cause of death in breast cancer. However, little is known about the dynamic changes during the evolvement of dissemination. In this study, 65 968 cells from four patients with breast cancer and paired metastatic axillary lymph nodes are profiled using single‐cell RNA sequencing (scRNA‐seq) and spatial transcriptomics. A disseminated cancer cell cluster with high levels of oxidative phosphorylation (OXPHOS), including the upregulation of cytochrome C oxidase subunit 6C and dehydrogenase/reductase 2, is identified. The transition between glycolysis and OXPHOS when dissemination initiates is noticed. Furthermore, this distinct cell cluster is distributed along the tumor's leading edge. The findings here are verified in three different cohorts of breast cancer patients and an external scRNA‐seq dataset, which includes eight patients with breast cancer and paired metastatic axillary lymph nodes. This work describes the dynamic metabolic evolvement of early disseminated breast cancer and reveals a switch between glycolysis and OXPHOS in breast cancer cells as the early event during lymph node metastasis. By single‐cell RNA sequencing and spatial transcriptomics, the early early‐disseminated breast cancer cells are found to travel from the border of primary tumor to axillary lymph nodes. During this metastasis, a switch between glycolysis and oxidative phosphorylation occurs in early disseminated breast cancer cells, indicating an interesting dynamic metabolic evolvement.