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Peer-reviewedCC BY 4.0Frontiers in Oncology

Spatial association of an AKR1C3-positive epithelial state with ACTA2-positive stromal cells and SPP1-positive macrophages in gastric cancer

  • Jingjing Yang1
  • Yixuan Dai1
  • Jianpeng Sheng2
  • Rong Xu1
  1. 1Zhangjiagang Hospital Affiliated to Soochow University/The First People's Hospital of Zhangjiagang City
  2. 2Multi-Omics Platform, Capital Medical University Innovation Center
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Abstract

Introduction: The spatial organization of epithelial states relative to stromal and myeloid cells in gastric cancer remains incompletely understood.

Methods: We integrated single-cell RNA-sequencing data from 36 normal and tumor tissue samples (GSE183904) with Visium spatial transcriptomics (GSE251950). Cell-state signatures were evaluated in TCGA-STAD (n = 375), and multiplex immunohistochemistry was performed on specimens from three patients.

Results: Epi4_AKR1C3 and FB3_ACTA2 showed nominal enrichment in tumor tissues, whereas Mac2_SPP1 showed no significant compositional difference between normal and tumor tissues. Higher signature scores for these three states were nominally associated with shorter overall survival (log-rank P = 0.044, 0.019, and 0.048, respectively), although none remained significant after multiple-testing correction. Spatial deconvolution identified regions of co-enrichment, and multiplex immunohistochemistry provided proof-of-concept evidence of close spatial proximity among the corresponding marker-defined populations.

Discussion: These findings identify a candidate AKR1C3-associated epithelial–stromal–myeloid spatial configuration in gastric cancer. Further mechanistic studies are needed to validate its biological and clinical significance.

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Cite

BibTeXRIS
BibTeX
@article{yang2026spatial,
  title = {{Spatial association of an AKR1C3-positive epithelial state with ACTA2-positive stromal cells and SPP1-positive macrophages in gastric cancer}},
  author = {Jingjing Yang and Yixuan Dai and Jianpeng Sheng and Rong Xu},
  journal = {Frontiers in Oncology},
  year = {2026},
  month = oct,
  doi = {10.3389/fonc.2026.1965632},
  url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1965632/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Spatial association of an AKR1C3-positive epithelial state with ACTA2-positive stromal cells and SPP1-positive macrophages in gastric cancer
AU  - Jingjing Yang
AU  - Yixuan Dai
AU  - Jianpeng Sheng
AU  - Rong Xu
PY  - 2026
DA  - 2026/10/28
JO  - Frontiers in Oncology
DO  - 10.3389/fonc.2026.1965632
UR  - https://www.frontiersin.org/articles/10.3389/fonc.2026.1965632/full
AB  - Introduction: The spatial organization of epithelial states relative to stromal and myeloid cells in gastric cancer remains incompletely understood.  Methods: We integrated single-cell RNA-sequencing data from 36 normal and tumor tissue samples (GSE183904) with Visium spatial transcriptomics (GSE251950). Cell-state signatures were evaluated in TCGA-STAD (n = 375), and multiplex immunohistochemistry was performed on specimens from three patients.  Results: Epi4_AKR1C3 and FB3_ACTA2 showed nominal enrichment in tumor tissues, whereas Mac2_SPP1 showed no significant compositional difference between normal and tumor tissues. Higher signature scores for these three states were nominally associated with shorter overall survival (log-rank P = 0.044, 0.019, and 0.048, respectively), although none remained significant after multiple-testing correction. Spatial deconvolution identified regions of co-enrichment, and multiplex immunohistochemistry provided proof-of-concept evidence of close spatial proximity among the corresponding marker-defined populations.  Discussion: These findings identify a candidate AKR1C3-associated epithelial–stromal–myeloid spatial configuration in gastric cancer. Further mechanistic studies are needed to validate its biological and clinical significance.
SN  - 2234-943X
ER  -