Single-cell RNA sequencing reveals distinct transcriptomic profiles and evolutionary patterns in lung cancer brain metastasis

Abstract

BackgroundLung cancer metastasis to the brain presents significant clinical challenges. Therefore, elucidating its underlying mechanisms and characterizing its transcriptomic landscape is essential for developing therapeutic interventions. MethodsWe analyzed two distinct single-cell RNA sequencing datasets of lung cancer metastasis to analyze the evolutionary trajectory of brain metastatic tumors. In addition, a systematic comparison of cell-cell interaction between tumor cells and lymphocytes was conducted within primary and brain metastatic tumors. ResultsThe brain metastatic tumors showed greater transcriptomic changes (reflected by a higher pseudotime) than tumors in the lymph nodes and primary tumors. Furthermore, our investigation has not only revealed specific shared ligand-receptor pairs in both mLN and mBrain, exemplified by the interaction between SPP1 and CD99 in T cells, but has also unveiled a diverse array of ligand-receptor pairs exclusive to the mBrain. Notably, this includes distinctive pairs such as APP and IL1 observed specifically in myeloid cells. ConclusionThe distinct microenvironment in the brain may influence the observed transcriptomic changes in tumors, emphasizing the significance of the specific environment in determining tumor behavior and therapeutic response.