Single-cell landscape reveals active cell subtypes and their interaction in the tumor microenvironment of gastric cancer

Abstract

Background: Gastric cancer remains the third most common cause of cancer-related death worldwide. The development of novel therapeutic strategies for gastric cancer requires a deep understanding of the tumor cells and microenvironment of gastric cancer. Methods: We performed the single-cell RNA sequencing (scRNA-seq) on nine untreated non-metastatic gastric cancer patients. The transcriptomic atlas and ligand-receptor-based intercellular communication networks of the single cells were characterized. Results: Here, we profiled the transcriptomes of 47,304 cells from nine patients with gastric cancer. Tregs cells were significantly enriched in the gastric tumor tissues with increased expression of immune suppression related genes, which suggest a more immunosuppressive microenvironment. We also observed the absence of separate exhausted CD8+ T cell cluster, and the low expression level of exhaustion markers PDCD1, CTLA4, HAVCR2, LAG-3, and TIGIT in those specific cells. These may serve as molecular-level evidence for the limited benefit of immunotherapy among gastric cancer patients. In addition, we found ACKR1 specifically expressed in tumor endothelial cells, associated with poor prognosis in the cohort data and potentially provided a novel target of gastric cancer treatment. Furthermore, the tight interaction between endothelial cells and fibroblast implied the important roles of fibroblast in tumor angiogenesis and the maintenance of tumor vasculature. Conclusions:In conclusion, this single-cell atlas provide understanding the cellular heterogeneity from molecular level in gastric cancer and will serve as a valuable resource for developing innovative early and companion diagnostics, as well as discovering novel targeted therapies for gastric cancer.

The molecular mechanisms of CTHRC1 in gastric cancer by integrating TCGA, GEO and GSA datasets

“…To verify the correlation between CTHRC1 and macrophages, we downloaded our previous scRNA-seq data from GSA for analysis. After identifying major cell types, we found 11 fibroblast clusters (F01-F11) from gastric cancer patients ( Li et al, 2022 ). In addition, F04 and F08 were significantly enriched in tumor samples, thus were denoted as three subsets of cancer associated fibroblasts (CAFs).…”

“…In our previous study (Li et al, 2022), F04 and F08 were significantly enriched in tumor samples, thus were denoted as (Tang et al, 2011), while TNFα is responsible for a diverse range of signaling events within cells, leading to necrosis or apoptosis, and also important for resistance to cancers (So and Ishii, 2019). In addition, Vecchi has reported that inhibiting AnxA1/ FPR1 autocrine axis can reduce breast cancer cell growth and aggressiveness both in vitro and in vivo (Vecchi et al, 2018).…”

“…In our previous study ( Li et al, 2022 ), F04 and F08 were significantly enriched in tumor samples, thus were denoted as three subsets of CAFs. Tang et al had indicated that GRN bound directly to tumor necrosis factor receptors (TNFRs) and disturbed the TNFα-TNFR interaction ( Tang et al, 2011 ), while TNFα is responsible for a diverse range of signaling events within cells, leading to necrosis or apoptosis, and also important for resistance to cancers ( So and Ishii, 2019 ).…”

“…In our previous study, we performed the scRNA-seq on nine untreated non-metastatic gastric cancer patients ( Li et al, 2022 ). A total of 47,304 cells with detectable expression of more than 200 genes were obtained after quality control.…”

Identification of a tissue resident memory CD8 T cell-related risk score signature for colorectal cancer, the association with TME landscapes and therapeutic responses

“…By analyzing scRNA-seq data obtained from small cell lung cancer patients, Tian et al (2022) recognized multiple T Cell clusters with markedly different immune checkpoint gene expression patterns, which provided rationale for the application of personalized ICI strategies to different patient groups. A generally immunosuppressive TME characterized by abundant Treg infiltration and the absence of exhausted CD8 T cells for gastric cancer (GC) patients was identified through the scRNA-seq analysis performed by Li Y. et al (2022) , which to some extent accounted for GC patients’ low response rate towards ICI treatment. Notably, in an article published recently, Song et al (2022) performed combinatorial analysis of single cell and bulk RNA-seq profiles and acquired some promising findings.…”