Multi-omics reveals tumor microenvironment heterogeneity and therapeutic vulnerabilities in peritoneal metastasis of gastric cancer
4 affiliations
- 1Department of Thyroid Surgery, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University
- 2Xiamen Municipal Key Laboratory of Gastrointestinal Oncology
- 3Department of Clinical Pharmacology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University
- 4Endoscopic Center, the First Affiliated Hospital, Fujian Medical University
Abstract
Peritoneal metastasis of gastric cancer (PMGC) is associated with a poor prognosis, with approximately one-third of patients presenting with peritoneal metastasis at diagnosis. Current systemic therapies have limited efficacy, underscoring the need for precise therapeutic targets in PMGC. We employed single-cell RNA sequencing (scRNA-seq) to characterize the cellular composition of the PMGC microenvironment, reconstruct epithelial cell developmental trajectories, and analyze intercellular communication networks. Spatial transcriptomics and multiplex immunohistochemistry were integrated to validate targets, and in vivo mouse models were used to assess therapeutic efficacy. Single-cell analysis identified a peritoneal metastasis (PM) signature associated with cancer cell differentiation origin and poor outcomes. We classified cancer cells as PM-high or PM-low based on this signature, with the PM-high group enriched in multiple oncogenic pathways and the PM-low group overexpressing CLDN18. Intercellular communication analyses showed epithelial cells and diverse subsets interact with regulatory T, natural killer, and proliferative T cells via PVR-TIGIT and NECTIN2-TIGIT. In vivo studies indicated that dual targeting of TIGIT and Claudin 18.2 (CLDN18.2) inhibited PMGC progression and ascites formation. These findings indicate that CLDN18.2 and TIGIT are potential therapeutic targets, whose combined inhibition suppresses PMGC progression and ascites formation, providing valuable insights for PMGC treatment.
Related
- Epigenetic rewiring of immunological memory in cancer: heterogeneity, mechanisms, and therapeutic vulnerabilities
- Bone Metastasis and the Immunosuppressive Tumor Microenvironment: Mechanisms and Therapeutic Strategies
- Intraperitoneal and Intravenous Paclitaxel Plus S-1 for Gastric Cancer With Peritoneal Metastasis
- Surgical Impact on Postoperative Morbidity in Colorectal Cancer with Peritoneal Metastasis: A Multicenter Prospective Observational Study.
- Integrative pan-cancer and clinical cytokine profiling reveals a pro-inflammatory cytokine index for colon cancer peritoneal metastasis and immunotherapy response
BibTeX
@article{xie2026multiomics,
title = {{Multi-omics reveals tumor microenvironment heterogeneity and therapeutic vulnerabilities in peritoneal metastasis of gastric cancer}},
author = {Wen Xie and Zhenfa Wang and Peiyu Lv and Jia Cheng and Lingyun Lin and Jingjing Hou and Xujin Wei and Kunzhai Huang and Huiqin Zhuo and Wangyu Cai},
journal = {Communications Biology},
year = {2026},
month = jun,
doi = {10.1038/s42003-026-10571-8},
url = {https://doi.org/10.1038/s42003-026-10571-8},
note = {CC BY},
}
RIS
TY - JOUR
TI - Multi-omics reveals tumor microenvironment heterogeneity and therapeutic vulnerabilities in peritoneal metastasis of gastric cancer
AU - Wen Xie
AU - Zhenfa Wang
AU - Peiyu Lv
AU - Jia Cheng
AU - Lingyun Lin
AU - Jingjing Hou
AU - Xujin Wei
AU - Kunzhai Huang
AU - Huiqin Zhuo
AU - Wangyu Cai
PY - 2026
DA - 2026/06/01
JO - Communications Biology
DO - 10.1038/s42003-026-10571-8
UR - https://doi.org/10.1038/s42003-026-10571-8
AB - Peritoneal metastasis of gastric cancer (PMGC) is associated with a poor prognosis, with approximately one-third of patients presenting with peritoneal metastasis at diagnosis. Current systemic therapies have limited efficacy, underscoring the need for precise therapeutic targets in PMGC. We employed single-cell RNA sequencing (scRNA-seq) to characterize the cellular composition of the PMGC microenvironment, reconstruct epithelial cell developmental trajectories, and analyze intercellular communication networks. Spatial transcriptomics and multiplex immunohistochemistry were integrated to validate targets, and in vivo mouse models were used to assess therapeutic efficacy. Single-cell analysis identified a peritoneal metastasis (PM) signature associated with cancer cell differentiation origin and poor outcomes. We classified cancer cells as PM-high or PM-low based on this signature, with the PM-high group enriched in multiple oncogenic pathways and the PM-low group overexpressing CLDN18. Intercellular communication analyses showed epithelial cells and diverse subsets interact with regulatory T, natural killer, and proliferative T cells via PVR-TIGIT and NECTIN2-TIGIT. In vivo studies indicated that dual targeting of TIGIT and Claudin 18.2 (CLDN18.2) inhibited PMGC progression and ascites formation. These findings indicate that CLDN18.2 and TIGIT are potential therapeutic targets, whose combined inhibition suppresses PMGC progression and ascites formation, providing valuable insights for PMGC treatment.
SN - 2399-3642
ER -