Single-cell RNA sequencing reveals epithelial cells driving brain metastasis in lung adenocarcinoma

Yonghui Wu; Fujun Yang; Shilan Luo; Xiang Li; Zhan Gu; Rui Fan; Yajuan Cao; Lixin Wang; Xiao Song

doi:10.1016/j.isci.2024.109258

Single-cell RNA sequencing reveals epithelial cells driving brain metastasis in lung adenocarcinoma

iScience. 2024 Feb 16;27(3):109258. doi: 10.1016/j.isci.2024.109258. eCollection 2024 Mar 15.

Authors

Yonghui Wu^{1

2}, Fujun Yang³, Shilan Luo⁴, Xiang Li³, Zhan Gu¹, Rui Fan¹, Yajuan Cao¹, Lixin Wang¹, Xiao Song³

Affiliations

¹ Department of Integrated Traditional Chinese and Western Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
² Graduate School of Shanghai University of Traditional Chinese Medicine, Shanghai, China.
³ Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
⁴ Department of Radiation Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.

Abstract

Brain metastases (BM) of lung adenocarcinoma (LUAD) are the most common intracranial malignancy leading to death. However, the cellular origins and drivers of BM from LUAD have not been clarified. Cellular composition was characterized by single-cell sequencing analysis of primary lung adenocarcinoma (pLUAD), BM and lymph node metastasis (LNM) samples in GSE131907. Our study briefly analyzed the tumor microenvironment (TME), focusing on the role of epithelial cells (ECs) in BM. We have discovered a population of brain metastasis-associated epithelial cells (BMAECs) expressing SPP1, SAA1, and CDKN2A, and it has been observed that this population is mainly composed of aneuploid cells from pLUAD, playing a crucial role in brain metastasis. Our study concluded that both LNM and BM in LUAD originated from pLUAD lesions, but there is currently insufficient evidence to prove a direct association between BM lesions and LNM lesions, which provides inspiration for further investigation of the TME in BM.

Keywords: Cancer; Cancer systems biology; Integrative aspects of cell biology; Transcriptomics.