Basic Study
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World J Gastrointest Oncol. Feb 15, 2025; 17(2): 97125
Published online Feb 15, 2025. doi: 10.4251/wjgo.v17.i2.97125
Landscape of four different stages of human gastric cancer revealed by single-cell sequencing
Xu-Shan Tang, Chun-Lei Xu, Na Li, Jian-Qing Zhang, Yong Tang
Xu-Shan Tang, Chun-Lei Xu, Na Li, Yong Tang, Department of Gastroenterology, Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi 830011, Xinjiang Uighur Autonomous Region, China
Jian-Qing Zhang, Department of Outpatient, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, Xinjiang Uighur Autonomous Region, China
Co-first authors: Xu-Shan Tang and Chun-Lei Xu.
Author contributions: Tang XS and Zhang JQ designed the research study; Xu CL and Li N performed the research; Tang XS, Zhang JQ and Tang Y provided assistance and advice on experiments; Xu CL, Li N, and Tang Y analyzed the data. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work. Tang XS and Xu CL contributed equally to this work as co-first authors.
Supported by Xinjiang Uygur Autonomous Region Natural Science Foundation, No. 2020D01C199.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of the Tumor Hospital Affiliated to Xinjiang Medical University (No. 2024-96).
Informed consent statement: All study participants or their legal guardian provided informed written consent about personal and medical data collection prior to study enrolment.
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: The dataset, technical appendix, and statistical code are available from the corresponding author at 2582471376@qq.com. Participants gave informed consent for data sharing, and all presented data are anonymized to ensure low risk of identification.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yong Tang, MD, Chief Doctor, Department of Gastroenterology, Tumor Hospital Affiliated to Xinjiang Medical University, No. 789 Suzhou East Street, Xinshi District, Urumqi 830011, Xinjiang Uighur Autonomous Region, China. 2582471376@qq.com
Received: May 23, 2024
Revised: October 12, 2024
Accepted: November 8, 2024
Published online: February 15, 2025
Processing time: 239 Days and 22.4 Hours
Abstract
BACKGROUND

Gastric cancer (GC) poses a substantial risk to human health due to its high prevalence and mortality rates. Nevertheless, current therapeutic strategies remain insufficient. Single-cell RNA sequencing (scRNA-seq) offers the potential to provide comprehensive insights into GC pathogenesis.

AIM

To explore the distribution and dynamic changes of cell populations in the GC tumor microenvironment using scRNA-seq techniques.

METHODS

Cancerous tissues and paracancerous tissues were obtained from patients diagnosed with GC at various stages (I, II, III, and IV). Single-cell suspensions were prepared and analyzed using scRNA-seq to examine transcriptome profiles and cell-cell interactions. Additionally, quantitative real-time polymerase chain reaction (qRT-PCR) and flow cytometry were applied for measuring the expression of cluster of differentiation (CD) 2, CD3D, CD3E, cytokeratin 19, cytokeratin 8, and epithelial cell adhesion molecules.

RESULTS

Transcriptome data from 73645 single cells across eight tissues of four patients were categorized into 25 distinct cell clusters, representing 10 different cell types. Variations were observed in these cell type distribution. The adjacent epithelial cells in stages II and III exhibited a degenerative trend. Additionally, the quantity of CD4 T cells and CD8 T cells were evidently elevated in cancerous tissues. Interaction analysis displayed a remarkable increase in interaction between B cells and other mast cells in stages II, III, and IV of GC. These findings were further validated through qRT-PCR and flow cytometry, demonstrating elevated T cells and declined epithelial cells within the cancerous tissues.

CONCLUSION

This study provides a comprehensive analysis of cell dynamics across GC stages, highlighting key interactions within the tumor microenvironment. These findings offer valuable insights for developing novel therapeutic strategies.

Keywords: Gastric cancer; Single-cell RNA sequencing; Tumor microenvironment; Cancer progression; Cell-cell interactions

Core Tip: Our single-cell atlas of gastric cancer (GC) is capable of providing a clearer view of the connection between the tumor microenvironment and paracancerous tissues, revealing the various cell progression in GC development and providing potential solutions for inhibiting cancer progression.