Relationships of tumor differentiation and immune infiltration in gastric cancers revealed by single-cell RNA-seq analyses

作者：Xin Zhou, Jingwei Yang, Yongqu Lu, Yanpeng Ma, Yan Meng, Qingqing Li, Junpeng Gao, Zhaoyu Jiang, Limei Guo, Wei Wang, Yun Liu, Lu Wen, Kai Miao, Wei Fu, Fuchou Tang · 发表于：Cellular and Molecular Life Sciences · 年份：2023 · DOI：10.1007/s00018-023-04702-1 · 被引用次数：33 · 研究领域：Cancer-related molecular mechanisms research、Single-cell and spatial transcriptomics、Cancer Immunotherapy and Biomarkers

Abstract Gastric cancers are highly heterogeneous malignant tumors. To reveal the relationship between differentiation status of cancer cells and tumor immune microenvironments in gastric cancer, single-cell RNA-sequencing was performed on normal mucosa tissue, differentiated gastric cancer (DGC) tissue, poorly differentiated gastric cancer (PDGC) tissue and neuroendocrine carcinoma (NEC) tissue sampled from surgically resected gastric cancer specimens. We identified the signature genes for both DGC and PDGC, and found that signature genes of PDGC strongly enriched in the epithelial–mesenchymal transition (EMT) program. Furthermore, we found that DGC tends to be immune-rich type whereas PDGC tends to be immune-poor type defined according to the density of tumor-infiltrating CD8 + T cells. Additionally, interferon alpha and gamma responding genes were specifically expressed in the immune-rich malignant cells compared with immune-poor malignant cells. Through analyzing the mixed adenoneuroendocrine carcinoma, we identified intermediate state malignant cells during the trans-differentiation process from DGC to NEC, which showed double-negative expressions of both DGC marker genes and NEC marker genes. Interferon-related pathways were gradually downregulated along the DGC to NEC trans-differentiation path, which was accompanied by reduced CD8 + cytotoxic T-cell infiltration. In summary, molecular features of both malignant cells and immune microenvironment cells of DGC, PDGC and ...