Language
English
Publication Date
2-14-2023
Journal
Nature Communications
DOI
10.1038/s41467-023-36310-9
PMID
36788228
PMCID
PMC9929081
PubMedCentral® Posted Date
2-14-2023
PubMedCentral® Full Text Version
Post-Print
Abstract
Peritoneal metastasis is the leading cause of death for gastrointestinal cancers. The native and therapy-induced ascites ecosystems are not fully understood. Here, we characterize single-cell transcriptomes of 191,987 ascites cancer/immune cells from 35 patients with/without gastric cancer peritoneal metastasis (GCPM). During GCPM progression, an increase is seen of monocyte-like dendritic cells (DCs) that are pro-angiogenic with reduced antigen-presenting capacity and correlate with poor gastric cancer (GC) prognosis. We also describe the evolution of monocyte-like DCs and regulatory and proliferative T cells following therapy. Moreover, we track GC evolution, identifying high-plasticity GC clusters that exhibit a propensity to shift to a high-proliferative phenotype. Transitions occur via the recently described, autophagy-dependent plasticity program, paligenosis. Two autophagy-related genes (MARCKS and TXNIP) mark high-plasticity GC with poorer prognosis, and autophagy inhibitors induce apoptosis in patient-derived organoids. Our findings provide insights into the developmental trajectories of cancer/immune cells underlying GCPM progression and therapy resistance.
Keywords
Humans, Ascites, Peritoneal Neoplasms, Peritoneum, Stomach Neoplasms, Gastric cancer, Cancer microenvironment, Cancer microenvironment
Published Open-Access
yes
Recommended Citation
Huang, Xuan-Zhang; Pang, Min-Jiao; Li, Jia-Yi; et al., "Single-Cell Sequencing of Ascites Fluid Illustrates Heterogeneity and Therapy-Induced Evolution During Gastric Cancer Peritoneal Metastasis" (2023). Faculty and Staff Publications. 1448.
https://digitalcommons.library.tmc.edu/baylor_docs/1448