Single-cell RNA sequencing reveals immune cell dysfunction in the peripheral blood of patients with highly aggressive gastric cancer

Rui Ma; Xuemeng Zhou; Xiaohui Zhai; Chuyue Wang; Rong Hu; You Chen; Liyang Shi; Xing Fang; Yuan Liao; Lifeng Ma; Mengmeng Jiang; Junqing Wu; Renying Wang; Jiao Chen; Taiyuan Cao; Ge Du; Yingying Zhao; Weili Wu; Haide Chen; Shanshan Li; Qizhou Lian; Guoji Guo; Jian Xiao; Andrew P Hutchins; Ping Yuan

doi:10.1111/cpr.13591

Single-cell RNA sequencing reveals immune cell dysfunction in the peripheral blood of patients with highly aggressive gastric cancer

Cell Prolif. 2024 Feb 6:e13591. doi: 10.1111/cpr.13591. Online ahead of print.

Authors

Rui Ma^{1

2}, Xuemeng Zhou³, Xiaohui Zhai⁴, Chuyue Wang^{1

2}, Rong Hu^{1

2}, You Chen^{1

2}, Liyang Shi³, Xing Fang^{5

6}, Yuan Liao⁵, Lifeng Ma⁵, Mengmeng Jiang⁷, Junqing Wu^{5

7}, Renying Wang⁵, Jiao Chen³, Taiyuan Cao⁴, Ge Du⁴, Yingying Zhao^{1

2}, Weili Wu^{1

2}, Haide Chen⁷, Shanshan Li⁴, Qizhou Lian^{8

9}, Guoji Guo^{5

6

7

10}, Jian Xiao¹¹, Andrew P Hutchins³, Ping Yuan^{1

2

12

13}

Affiliations

¹ Guangdong Institute of Gastroenterology, Guangzhou, China.
² Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
³ Shenzhen Key Laboratory of Gene Regulation and Systems Biology, Department of Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China.
⁴ Department of Medical Oncology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
⁵ Center for Stem Cell and Regenerative Medicine, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
⁶ Zhejiang Provincial Key Lab for Tissue Engineering and Regenerative Medicine, Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Hangzhou, China.
⁷ Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China.
⁸ Faculty of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
⁹ Guangzhou Institute of Eugenics and Perinatology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
¹⁰ Institute of Hematology, Zhejiang University, Hangzhou, China.
¹¹ Department of Medical Oncology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China.
¹² Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
¹³ Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

PMID: 38319150
DOI: 10.1111/cpr.13591

Abstract

Highly aggressive gastric cancer (HAGC) is a gastric cancer characterized by bone marrow metastasis and disseminated intravascular coagulation (DIC). Information about the disease is limited. Here we employed single-cell RNA sequencing to investigate peripheral blood mononuclear cells (PBMCs), aiming to unravel the immune response of patients toward HAGC. PBMCs from seven HAGC patients, six normal advanced gastric cancer (NAGC) patients, and five healthy individuals were analysed by single-cell RNA sequencing. The expression of genes of interest was validated by bulk RNA-sequencing and ELISA. We found a massive expansion of neutrophils in PBMCs of HAGC. These neutrophils are activated, but immature. Besides, mononuclear phagocytes exhibited an M2-like signature and T cells were suppressed and reduced in number. Analysis of cell-cell crosstalk revealed that several signalling pathways involved in neutrophil to T-cell suppression including APP-CD74, MIF-(CD74+CXCR2), and MIF-(CD74+CD44) pathways were increased in HAGC. NETosis-associated genes S100A8 and S100A9 as well as VEGF, PDGF, FGF, and NOTCH signalling that contribute to DIC development were upregulated in HAGC too. This study reveals significant changes in the distribution and interactions of the PBMC subsets and provides valuable insight into the immune response in patients with HAGC. S100A8 and S100A9 are highly expressed in HAGC neutrophils, suggesting their potential to be used as novel diagnostic and therapeutic targets for HAGC.

Abstract

Grants and funding