1557P - Single-cell RNA-seq dissecting the initiating liver metastasis cells and liver metastatic microenvironment in gastric cancer

Background

Liver metastasis (LM) frequently occurs in patients with advanced gastric cancer; yet our understanding of the underlying salient biology is preliminary. Here, we performed single-cell RNA-seq in two patients with LM of gastric cancer to explore the initiating liver metastasis cells and liver metastatic microenvironment in gastric cancer.

Methods

Single cell RNA sequencing was performed on tissues from LM of gastric cancer. Also, we downloaded the single-cell RNA-seq of hepatocellular carcinoma (HCC) and primary gastric cancer from GEO database. Seurat were applied to sort single-cell RNA-seq of LM in gastric cancer and primary gastric cancer into different clusters via feature dimension reduction and then we investigated their expression profiling, stemness initiating and enrichment pathways. Furthermore, CellChat and monocle2 were used to explore the cellular communication and regulatory network of liver metastatic microenvironment.

Results

The transcriptomes of 13305, 26373, 20207 single cells among LM of gastric cancer, HCC, and primary gastric cancer were extracted respectively. There were 14 clusters divided into epithelial cells of liver metastasis single cells. Differential gene analyses and ratio analyses in LM and corresponding primary cancers groups showed that C10 and C12 might be the LM initiating cells clusters. And they were both enriched in the positive regulation of cell migration. SOX6⁺ MMP7⁺ epithelial cells might be the LM initiating cells in gastric cancer. Cell communication and inverse temporal analysis showed that SEPP1⁺ macrophage and CXCL2⁺ cancer associated fibroblasts (CAFs) might regulate metastatic microenvironment, of which promoted cancer stem cells migration.

Conclusions

The initiating liver metastasis cells and liver metastatic microenvironment in gastric cancer have been investigated in this study, which provided a further understanding of the potential biological mechanisms of LM in gastric cancer.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

National Natural Science National Natural Science Foundation of China.

Disclosure

All authors have declared no conflicts of interest.