Identification of RAC1 in promoting brain metastasis of lung adenocarcinoma using single-cell transcriptome sequencing

作者：Mingyu Chen, Hanyue Li, Xiaolin Xu, Xunxia Bao, Lei Xue, Xinghao Ai, Jian Xu, Ming Xu, Yong Shi, Timing Zhen, Jie Li, Yi Yang, Yang Ji, Zhiliang Fu, Kaichen Xing, Tao Qing, Qiubo Wang, Ping Zhong, Sibo Zhu · 发表于：Cell Death and Disease · 年份：2023 · DOI：10.1038/s41419-023-05823-y · 被引用次数：35 · 研究领域：Brain Metastases and Treatment、RNA modifications and cancer、Cancer-related molecular mechanisms research

This study aims to give a new perspective to the biomarkers in the lung adenocarcinoma (LUAD) brain metastasis, pathways involved and potential therapeutics. We performed a comprehensive single-cell level transcriptomic analysis on one LUAD patient with circulating tumor cells (CTCs), primary tumor tissue and metastatic tumor tissue using scRNA-seq approach to identify metastasis related biomarkers. Further scRNA-seq were performed on 7 patients to validate the cancer metastatic hallmark. with single cells collected from either metastatic or primary LUAD tissues. Pathological and functional studies were also performed to evidence the critical role of RAC1 in the LUAD metastasis. Hallmark gene was verified based on immunohistochemistry staining, cytological experiment, survival information from The Cancer Genome Atlas (TCGA), and staining results from Human Protein Atlas (HPA) databases. PCA analysis revealed that CTCs were in the intermediate place between the metastatic group and primary group. In the unsupervised clustering analysis CTCs were closer to one of the metastatic tumor cells, implying heterogeneity of the metastatic tumor and origin of the CTCs were from metastatic site. Transitional phase related gene analysis identified RAC1 was enriched in metastatic tumor tissue (MTT) preferred gene set functioning as regulated cell death and apoptosis as well as promoted macromolecule organization. Compared with normal tissue, expression levels of RAC1 increased significantl...