Single-cell RNA sequencing reveals cell heterogeneity and transcriptome profile of breast cancer lymph node metastasis

Kun Xu; Runtian Wang; Hui Xie; Longfei Hu; Cong Wang; Jiali Xu; Chengjun Zhu; Yiqiu Liu; Fangyan Gao; Xintong Li; Cenzhu Wang; Jinyi Huang; Wenbin Zhou; Guohua Zhou; Yongqian Shu; Xiaoxiang Guan

doi:10.1038/s41389-021-00355-6

Single-cell RNA sequencing reveals cell heterogeneity and transcriptome profile of breast cancer lymph node metastasis

Oncogenesis. 2021 Oct 5;10(10):66. doi: 10.1038/s41389-021-00355-6.

Authors

Kun Xu^#¹, Runtian Wang^#¹, Hui Xie^#², Longfei Hu^#³, Cong Wang⁴, Jiali Xu¹, Chengjun Zhu¹, Yiqiu Liu¹, Fangyan Gao¹, Xintong Li¹, Cenzhu Wang¹, Jinyi Huang¹, Wenbin Zhou², Guohua Zhou⁵, Yongqian Shu⁶, Xiaoxiang Guan^{7

8}

Affiliations

¹ Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
² Department of Breast Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
³ Singleron Biotechnologies, Yaogu Avenue 11, Nanjing, Jiangsu, China.
⁴ Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
⁵ Department of Pharmacology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China. ghzhou@nju.edu.cn.
⁶ Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. shuyongqian@csco.org.cn.
⁷ Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. xguan@njmu.edu.cn.
⁸ Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, Nanjing, China. xguan@njmu.edu.cn.

^# Contributed equally.

Abstract

Molecular mechanisms underlying breast cancer lymph node metastasis remain unclear. Using single-cell sequencing, we investigated the transcriptome profile of 96,796 single cells from 15 paired samples of primary tumors and axillary lymph nodes. We identified nine cancer cell subclusters including CD44 + / ALDH2 + /ALDH6A1 + breast cancer stem cells (BCSCs), which had a copy-number variants profile similar to that of normal breast tissue. Importantly, BCSCs existed only in primary tumors and evolved into metastatic clusters infiltrating into lymph nodes. Furthermore, transcriptome data suggested that NECTIN2-TIGIT-mediated interactions between metastatic breast cancer cells and tumor microenvironment (TME) cells, which promoted immune escape and lymph node metastasis. This study is the first to delineate the transcriptome profile of breast cancer lymph node metastasis using single-cell RNA sequencing. Our findings offer novel insights into the mechanisms underlying breast cancer metastasis and have implications in developing novel therapies to inhibit the initiation of breast cancer metastasis.