Single-cell transcriptome analysis reveals heterogeneity of neutrophils in non-small cell lung cancer
Yunzhen Wang1, Ziyi Zhu1, Raojun Luo1
1Department of Thoracic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Background:
Lung cancer stands out as a highly perilous malignant tumor with severe implications for human health. There has been a growing interest in neutrophils as a result of their role in promoting cancer in recent years. Thus, the present study aimed to investigate the heterogeneity of neutrophils in non-small cell lung cancer (NSCLC).
Methods:
Single-cell RNA sequencing of tumor-associated neutrophils (TANs) and polymorphonuclear neutrophils sourced from the Gene Expression Omnibus database was analyzed. Moreover, cell-cell communication, differentiation trajectories and transcription factor analyses were performed.
Results:
Neutrophils were found to be closely associated with macrophages. Four major types of TANs were identified: a transitional subcluster that migrated from blood to tumor microenvironment (TAN-0), an inflammatory subcluster (TAN-1), a subpopulation that displayed a distinctive transcriptional signature (TAN-2) and a final differentiation state that promoted tumor formation (TAN-3). Meanwhile, TAN-3 displayed a marked increase in glycolytic activity. Finally, transcription factors were analyzed to uncover distinct TAN cluster-specific regulons.
Conclusions:
The discovery of the dynamic characteristics of TANs in the present study is anticipated to contribute to yielding a better understanding of the tumor microenvironment and advancing the treatment of NSCLC.
