Reconstruction of the gastric cancer microenvironment after neoadjuvant chemotherapy by longitudinal single-cell sequencing

作者：Yingtai Chen, Jianhua Yin, Lulu Zhao, Guangyu Zhou, Shichen Dong, Yueming Zhang, Penghui Niu, Hu Ren, Tianjiao Zheng, Juan Yan, Wenbin Li, Peiqin Ma, Cuijuan Zhang, Wei Chen, George M. Church, Guibo Li, Dongbing Zhao · 发表于：Journal of Translational Medicine · 年份：2022 · DOI：10.1186/s12967-022-03792-y · 被引用次数：24 · 研究领域：Single-cell and spatial transcriptomics、Ferroptosis and cancer prognosis、Cancer Immunotherapy and Biomarkers

BACKGROUND: Little is known on the tumor microenvironment (TME) response after neoadjuvant chemotherapy (NACT) in gastric cancer on the molecular level. METHODS: Here, we profiled 33,589 cell transcriptomes in 14 samples from 11 gastric cancer patients (4 pre-treatment samples, 4 post-treatment samples and 3 pre-post pairs) using single-cell RNA sequencing (scRNA-seq) to generate the cell atlas. The ligand-receptor-based intercellular communication networks of the single cells were also characterized before and after NACT. RESULTS: Compered to pre-treatment samples, CD4+ T cells (P = 0.018) and CD8+ T cells (P = 0.010) of post-treatment samples were significantly decreased, while endothelial cells and fibroblasts were increased (P = 0.034 and P = 0.005, respectively). No significant difference observed with respect to CD4+ Tregs cells, cycling T cells, B cells, plasma cells, macrophages, monocytes, dendritic cells, and mast cells (P > 0.05). In the unsupervised nonnegative matrix factorization (NMF) analysis, we revealed that there were three transcriptional programs (NMF1, NMF2 and NMF3) shared among these samples. Compared to pre-treatment samples, signature score of NMF1 was significantly downregulated after treatment (P = 0.009), while the NMF2 signature was significantly upregulated after treatment (P = 0.013). The downregulated NMF1 and upregulated NMF2 signatures were both associated with improved overall survival outcomes based on The Cancer Genome Atlas (TCGA) databa...