Single-cell and bulk transcriptome-based identification of myeloid-derived suppressor cell-associated immune evasion signatures and a prognostic model for gastric cancer.
8 affiliations
- 1Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China. [email protected].
- 2State Key Laboratory of Digestive Health, Beijing, China. [email protected].
- 3National Clinical Research Center for Digestive Disease, Beijing, China. [email protected].
- 4Beijing Key Laboratory of Early Gastrointestinal Cancer Medicine and Medical Devices, Beijing, China. [email protected].
- 5Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
- 6State Key Laboratory of Digestive Health, Beijing, China.
- 7National Clinical Research Center for Digestive Disease, Beijing, China.
- 8Beijing Key Laboratory of Early Gastrointestinal Cancer Medicine and Medical Devices, Beijing, China.
Abstract
Background
Gastric cancer (GC) immunotherapy has limited efficacy. We developed a myeloid immunosuppressive niche score (GC-MIS) to quantify immune evasion and assess its association with the tumor microenvironment and patient prognosis.Methods
Two single-cell and three bulk transcriptomic cohorts were analyzed. A 12-gene MDSC-like signature (MIS) and an 8-gene tumor-intrinsic (TU) module were identified, and GC-MIS was defined as the standardized composite score of the two. Bulk cohort analyses included multivariable regression, Cox modeling, and prognostic evaluation (AUC, C-index, calibration, and decision curves). CellChat characterized epithelial-myeloid interactions, and in vitro GC cell lines exposed to inflammatory and hypoxic stimuli with pathway-specific inhibitors were assessed for PD-L1, STAT3 phosphorylation, and chemokine responses.Results
MIS and TU modules were stable and moderately correlated at the single-cell level. In bulk cohorts, GC-MIS was positively associated with T-cell exhaustion and myeloid abundance, and inversely associated with antigen presentation (adjusted R² = 0.33-0.41). High GC-MIS independently predicted worse survival (pooled HR = 1.32, P < 0.001). A GC-MIS-based model combined with clinical variables showed consistent but moderate prognostic performance across cohorts (5-year AUC ≈ 0.66). Pathway analyses implicated JAK-STAT, HIF-1, and PD-1/PD-L1 signaling, and GC-MIS correlated with CXCL8, IL6, and CCL2 communication axes. In vitro, inflammatory and hypoxic stimuli induced PD-L1 and STAT3 activation, which were significantly attenuated by targeted inhibitors (P < 0.05).Conclusions
GC-MIS is a reproducible transcriptional score associated with features of the tumor immune microenvironment and prognosis in gastric cancer. It reflects tumor-myeloid interaction programs and may serve as a prognostic biomarker. The associated inflammatory and hypoxia-linked signaling pathways warrant further investigation in functional and immunotherapy-treated cohorts.
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BibTeX
@article{zhang2026singlecell,
title = {{Single-cell and bulk transcriptome-based identification of myeloid-derived suppressor cell-associated immune evasion signatures and a prognostic model for gastric cancer.}},
author = {Xinghua Zhang and Can Sun and Xi Zhang},
journal = {BMC cancer},
year = {2026},
month = jul,
doi = {10.1186/s12885-026-16584-0},
url = {https://europepmc.org/article/MED/42928204},
note = {CC BY},
}
RIS
TY - JOUR
TI - Single-cell and bulk transcriptome-based identification of myeloid-derived suppressor cell-associated immune evasion signatures and a prognostic model for gastric cancer.
AU - Xinghua Zhang
AU - Can Sun
AU - Xi Zhang
PY - 2026
DA - 2026/07/29
JO - BMC cancer
DO - 10.1186/s12885-026-16584-0
UR - https://europepmc.org/article/MED/42928204
AB - Background Gastric cancer (GC) immunotherapy has limited efficacy. We developed a myeloid immunosuppressive niche score (GC-MIS) to quantify immune evasion and assess its association with the tumor microenvironment and patient prognosis.Methods Two single-cell and three bulk transcriptomic cohorts were analyzed. A 12-gene MDSC-like signature (MIS) and an 8-gene tumor-intrinsic (TU) module were identified, and GC-MIS was defined as the standardized composite score of the two. Bulk cohort analyses included multivariable regression, Cox modeling, and prognostic evaluation (AUC, C-index, calibration, and decision curves). CellChat characterized epithelial-myeloid interactions, and in vitro GC cell lines exposed to inflammatory and hypoxic stimuli with pathway-specific inhibitors were assessed for PD-L1, STAT3 phosphorylation, and chemokine responses.Results MIS and TU modules were stable and moderately correlated at the single-cell level. In bulk cohorts, GC-MIS was positively associated with T-cell exhaustion and myeloid abundance, and inversely associated with antigen presentation (adjusted R² = 0.33-0.41). High GC-MIS independently predicted worse survival (pooled HR = 1.32, P < 0.001). A GC-MIS-based model combined with clinical variables showed consistent but moderate prognostic performance across cohorts (5-year AUC ≈ 0.66). Pathway analyses implicated JAK-STAT, HIF-1, and PD-1/PD-L1 signaling, and GC-MIS correlated with CXCL8, IL6, and CCL2 communication axes. In vitro, inflammatory and hypoxic stimuli induced PD-L1 and STAT3 activation, which were significantly attenuated by targeted inhibitors (P < 0.05).Conclusions GC-MIS is a reproducible transcriptional score associated with features of the tumor immune microenvironment and prognosis in gastric cancer. It reflects tumor-myeloid interaction programs and may serve as a prognostic biomarker. The associated inflammatory and hypoxia-linked signaling pathways warrant further investigation in functional and immunotherapy-treated cohorts.
SN - 1471-2407
ER -