Abstract 1557P
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.
Resources from the same session
1489P - To investigate the differences in efficacy between immunotherapy and combined immunotherapy in elderly patients with non-small cell lung cancer
Presenter: Ye Mao
Session: Poster session 21
1490P - Removal of TNF-Rs frees TNF-α’s anticancer activity alone or in combination chemo- or immunotherapy in advanced NSCLC
Presenter: Mustafa Bozkurt
Session: Poster session 21
1491P - PD-L1 TPS ≥50% predicts durable response after discontinuing immune checkpoint inhibitors in metastatic non-small cell lung cancer patients
Presenter: Jeongmin Seo
Session: Poster session 21
1493P - A phase II, multi-center, open-label, dose-optimization study evaluating telomere targeting agent THIO sequenced with cemiplimab in patients with advanced NSCLC: Preliminary results
Presenter: Tomasz Jankowski
Session: Poster session 21
1495P - Cemiplimab plus chemotherapy versus chemotherapy in non-small cell lung cancer with PD-L1 ≥1%: EMPOWER-Lung 3 results
Presenter: Ana Baramidze
Session: Poster session 21
1496P - Higher levels of CSF-1 support resistance to immune checkpoint inhibitors in advanced non-small cell lung cancer
Presenter: Paul Takam Kamga
Session: Poster session 21
1497P - Gut microbiome is associated with the clinical response to anti-PD-1 based immunotherapy in untreated advanced non-small-cell lung cancer
Presenter: Yawen Bin
Session: Poster session 21