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  3. Spatial omics study reveals molecular-cellular dynamics of tumor ecosystem in esophageal squamous-cell carcinoma initiation and progression

Spatial omics study reveals molecular-cellular dynamics of tumor ecosystem in esophageal squamous-cell carcinoma initiation and progression

  • Cell Rep Med. 2026 Mar 17;7(3):102650. doi: 10.1016/j.xcrm.2026.102650.
Zhao Liu 1,  Wenhao Zhou 2,  Lei Li 3,  Congcong Song 2,  Meng Yue 4,  Huilai Lv 1,  Zhenhua Li 1,  Minghao Zhang 1,  Na Li 2,  Jiaqian Wang 2,  Lianmei Zhao 5,  Haitao Luo 6,  Ziqiang Tian 7
Affiliations

Affiliations

  • 1 Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050017, China.
  • 2 Kindstar Global Precision Medicine Institute, Shenzhen 518000, China.
  • 3 Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050017, China.
  • 4 Pathology Department, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050017, China.
  • 5 Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050017, China. Electronic address: [email protected].
  • 6 Kindstar Global Precision Medicine Institute, Shenzhen 518000, China. Electronic address: [email protected].
  • 7 Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050017, China. Electronic address: [email protected].
PMID: 41791392 DOI: 10.1016/j.xcrm.2026.102650
Abstract

Deciphering the molecular and cellular dynamics during esophageal squamous-cell carcinoma (ESCC) evolution is critical for elucidating the underlying disease mechanisms and devising rational targeted therapeutic strategies. Here, we perform digital spatial profiling on 32 tissue samples from 18 patients across different ESCC stages. At ESCC initiation, tumor cells undergo coordinated regulation of epidermal development and keratinocyte differentiation, accompanied by increased B cells and decreased T cells. In late stages, the phosphatidylinositol 3-kinase-protein kinase B (PI3K/Akt) pathway is continuously upregulated, and tertiary lymphoid structures are dysregulated. We further verify these findings by multiplex immunofluorescence. Notably, the O-GlcNAc transferase gene, activated exclusively in late stages, correlates with poor prognosis, and its knockdown inhibits ESCC cell migration and invasion. In summary, this study unravels ESCC ecosystem evolution mechanisms via spatial omics, providing a roadmap for precision therapeutics.

Keywords

O-GlcNAc transferase; PI3K/AKT signaling; digital spatial profiling; esophageal squamous cell carcinoma; esophageal squamous precancerous lesions; spatial omics; tertiary lymphoid structures; tumor microenvironment.

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