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

Bin Wang, Yingyi Zhang, Tao Qing, Kaichen Xing, Jie Li, Timing Zhen, Sibo Zhu, Xianbao Zhan
Author Information
  1. Bin Wang: Department of Oncology, Changhai Hospital, Second Military Medical University, No. 168 Changhai Road, Shanghai, 200433, China.
  2. Yingyi Zhang: Department of Oncology, Changhai Hospital, Second Military Medical University, No. 168 Changhai Road, Shanghai, 200433, China.
  3. Tao Qing: School of Life Sciences, Fudan University, No. 2005 Songhu Road, Shanghai, 200438, China.
  4. Kaichen Xing: Shanghai Cinoasia Institute, Shanghai, 200438, China.
  5. Jie Li: Shanghai Cinoasia Institute, Shanghai, 200438, China.
  6. Timing Zhen: Shanghai Cinoasia Institute, Shanghai, 200438, China.
  7. Sibo Zhu: School of Life Sciences, Fudan University, No. 2005 Songhu Road, Shanghai, 200438, China. sibozhu@fudan.edu.cn.
  8. Xianbao Zhan: Department of Oncology, Changhai Hospital, Second Military Medical University, No. 168 Changhai Road, Shanghai, 200433, China. zhanxianbao@csco.org.cn.

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.

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MeSH Term

Aged
Female
Gene Expression Regulation, Neoplastic
Humans
Lymphatic Metastasis
Male
Middle Aged
RNA-Seq
Single-Cell Analysis
Stomach Neoplasms