2. Academic Validation
  3. SPTSSA facilitates gastric cancer progression with modulating PD-L1 in immunomicroenvironment through Wnt/β-catenin pathway

SPTSSA facilitates gastric cancer progression with modulating PD-L1 in immunomicroenvironment through Wnt/β-catenin pathway

  • Cell Oncol (Dordr). 2025 Aug;48(4):1127-1144. doi: 10.1007/s13402-025-01072-7.
Pingping Sun # 1 2,  Weiwei Qin # 1 3,  Haiyan Xu 1,  Hang Yin 1,  Lei Yang 1 2,  Xiaojing Zhang 1 2,  Xiaoxia Jin 4,  Qiang Xu 4,  Han Wu 5,  Xiaoling Kuai 6,  Lizhou Jia 7,  Jianfei Huang 8 9,  Yao Wang 10
Affiliations

Affiliations

  • 1 Department of Clinical and Translational Research Center, Affiliated Hospital of Nantong University & Medical School of Nantong University, Nantong, Jiangsu, China.
  • 2 Institute of Oncology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
  • 3 Department of Pathology, Haian Hospital of Traditional Chinese Medicine, Nantong, Jiangsu, China.
  • 4 Department of Pathology, Nantong Tumor Hospital Affiliated to Nantong University, Nantong, Jiangsu, China.
  • 5 Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
  • 6 Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
  • 7 Basic Medical Sciences College, Inner Mongolia Medical University, Hohhot, China.
  • 8 Department of Clinical and Translational Research Center, Affiliated Hospital of Nantong University & Medical School of Nantong University, Nantong, Jiangsu, China. jfhuang@ntu.edu.cn.
  • 9 Institute of Oncology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China. jfhuang@ntu.edu.cn.
  • 10 Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China. wangyao@ntu.edu.cn.
  • # Contributed equally.
PMID: 40498284 DOI: 10.1007/s13402-025-01072-7
Abstract

Purpose: Gastric Cancer (GC) remains a considerable global health concern, underscoring the necessity for dependable biomarkers for its diagnosis and treatment. This investigation seeks to investigate the clinical predictive value and functional roles of SPTSSA in GC.

Methods: The mRNA expression of SPT family molecules was analyzed through bioinformatics approaches. In vitro and in vivo studies assessed the function of SPTSSA in the malignant progression of GC. Additionally, SPTSSA protein levels in GC tissues and peripheral venous blood were measured using immunofluorescence staining and enzyme-linked immunosorbent assay, respectively. The link between SPTSSA expression and immune cell infiltration in GC was also evaluated by multiplex immunohistochemistry.

Results: Patients exhibiting elevated levels of SPTSSA mRNA experienced the poorest prognosis in comparison to Other members of the SPT family. SPTSSA overexpression enhanced the malignant phenotype of GC in in vitro and in vivo experiments. Mechanistically, SPTSSA facilitated the accumulation of β-catenin and the transcription of programmed death ligand 1 (PD-L1) through the Wnt signaling pathway. SPTSSA protein levels were markedly elevated in both GC tissues and peripheral venous blood. Furthermore, increased expression of SPTSSA was linked to a reduction in CD8+ T cell infiltration, heightened M2 macrophage infiltration, and increased PD-L1 expression in GC patients.

Conclusion: SPTSSA promotes GC progression by modulating PD-L1 expression in immunomicroenvironment via the Wnt signaling pathway. Consequently, SPTSSA emerges as a promising new prognostic indicator and a potential therapeutic target for GC management.

Keywords

Gastric cancer; PD-L1; Prognosis; SPTSSA; Wnt signaling pathway.

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