ArticleJournal of gastroenterology and hepatology2025
Unraveling the Role of Programmed Cell Death Gene Signature and THBS1 in Gastric Cancer Progression and Therapy Response.
Article in Journal of gastroenterology and hepatology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Vascular SMC-like CAF-derived THBS1 drives tumor-associated neutrophil recruitment to orchestrate an immunosuppressive microenvironment in gastric cancer.Cell death & disease · 2026Article
- Glycosylation-Related Gene Signature Identifies MFNG as a Key Driver of Proliferation and Metastasis in Colorectal Cancer.OncoTargets and therapy · 2026Article
- Unraveling the Role of Programmed Cell Death Gene Signature and THBS1 in Gastric Cancer Progression and Therapy Response.Journal of gastroenterology and hepatology · 2025Article
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Authors and funding
11 authors.
Funding
Abstract
backgroundProgrammed cell death (PCD) genes play crucial roles in cancer progression and response to therapies, yet their impact on gastric cancer remains inadequately elucidated. This study aimed to create a prognostic cell death signature (PCDs) for gastric cancer, providing insights into potential therapeutic targets and survival predictors.
methodsWe utilized TCGA-STAD and five GEO datasets, representing thousands of gastric cancer samples, for a comprehensive analysis of PCD genes. Differential gene expression, functional enrichment, survival, and machine learning analyses were conducted to construct a PCD-based prognostic model.
resultsA total of 249 differentially expressed PCD genes were identified between cancerous and noncancerous gastric tissues. Subsequently, a PCD signature based on seven genes was developed and cross-validated across multiple cohorts. The high-PCD subtype correlated with poorer survival outcomes, lower tumor mutational burden, higher infiltration of M2 macrophages, lower levels of immune checkpoint expression, and decreased response to immunotherapy. A nomogram incorporating the PCDs provided accurate survival rate predictions. Additionally, nine machine learning algorithms were implemented for recurrence prediction, with the random forest model displaying high effectiveness. In this model, thrombospondin 1 (THBS1) showed the highest weight, and its knockdown significantly reduced gastric cancer cell proliferation and invasion.
conclusionThis study underscores the significance of PCD genes, particularly THBS1, in gastric cancer progression and highlights their value as potential therapeutic targets. The predictive models developed here can aid in assessing patient prognosis and tailoring personalized treatment strategies.
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