Comprehensive analysis of metastatic gastric cancer tumour cells using single-cell RNA-seq

Bin Wang,Xianbao Zhan,Jie Li,Kaichen Xing,Sibo Zhu,Yingyi Zhang,Tao Qing,Timing Zhen

doi:10.1038/s41598-020-80881-2

Abstract

Gastric cancer (GC) is a leading cause of cancer-induced mortality, with poor prognosis with metastasis. The mechanism of gastric carcinoma lymph node metastasis remains unknown due to traditional bulk-leveled approaches masking the roles of subpopulations. To answer questions concerning metastasis from the gastric carcinoma intratumoural perspective, we performed single-cell level analysis on three gastric cancer patients with primary cancer and paired metastatic lymph node cancer tissues using single-cell RNA-seq (scRNA-seq). The results showed distinct carcinoma profiles from each patient, and diverse microenvironmental subsets were shared across different patients. Clustering data showed significant intratumoural heterogeneity. The results also revealed a subgroup of cells bridging the metastatic group and primary group, implying the transition state of cancer during the metastatic process. In the present study, we obtained a more comprehensive picture of gastric cancer lymph node metastasis, and we discovered some GC lymph node metastasis marker genes (ERBB2, CLDN11 and CDK12), as well as potential gastric cancer evolution-driving genes (FOS and JUN), which provide a basis for the treatment of GC.

Highlights

Gastric cancer (GC) is a leading cause of cancer-induced mortality, with poor prognosis with metastasis
Genomic analysis revealed a series of significant actionable mutation loads or pathways in gastric cancer, such as PI3K/ AKT/mTOR, CLD18, and HER2/EGFR, which are likely to induce primary gastric cancer to develop into metastases[6,7]
The mechanism of gastric carcinoma lymph node metastasis remains unknown, partly because data from metastasis studies were generated with the bulk approach, which were likely to mask the roles of subpopulations

Summary

Introduction

Gastric cancer (GC) is a leading cause of cancer-induced mortality, with poor prognosis with metastasis. The mechanism of gastric carcinoma lymph node metastasis remains unknown due to traditional bulk-leveled approaches masking the roles of subpopulations. To answer questions concerning metastasis from the gastric carcinoma intratumoural perspective, we performed singlecell level analysis on three gastric cancer patients with primary cancer and paired metastatic lymph node cancer tissues using single-cell RNA-seq (scRNA-seq). The mechanism of gastric carcinoma lymph node metastasis remains unknown, partly because data from metastasis studies were generated with the bulk approach, which were likely to mask the roles of subpopulations. ScRNA-seq can be employed in analysing different degrees of GC, which is a potential good predictor of GC prognosis[16] These studies have paid attention to the tumour heterogeneity of GC but lack research on GC csco.org.cn. Clinical characteristics Numbers of analysis cells (TT/LN) Age Sex Histopathological diagnosis Pathological stage T N M Site of origin Infiltration degree Tumour size (cm) CEA (ng/mL) CA724 (U/mL) CA199 (U/mL) HER2 IHC HER2 FISH HER2/CSP17 Ki67 P53

Methods

Results

Conclusion