{"title":"Development and validation of a gastric cancer prognostic model utilizing lymphatic endothelial cell-related genes.","authors":"Sijie Sun, Jieyun Zhang, Weijian Guo","doi":"10.1186/s13000-025-01683-6","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer is one of the most common cancers worldwide, with its prognosis influenced by factors such as tumor clinical stage, histological type, and the patient's overall health. Recent studies highlight the critical role of lymphatic endothelial cells (LECs) in the tumor microenvironment. Perturbations in LEC function in gastric cancer, marked by aberrant activation or damage, disrupt lymphatic fluid dynamics and impede immune cell infiltration, thereby modulating tumor progression and patient prognosis. Hence, we aimed to construct a prognostically discriminative model group in LECs-related factors.</p><p><strong>Methods: </strong>Gene expression and clinical data of gastric cancer patients were obtained from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Fudan University Shanghai Cancer Center (FUSCC). Using the Wilcoxon test, we assessed the relationship between LECs, angiogenesis, and the immunological milieu. Differentially expressed and prognostically significant LEC-associated genes were identified through \"limma\" R package-assisted analysis coupled with univariate Cox analysis. A prognostic model was developed, and LEC-associated gene signatures were refined through least absolute shrinkage and selection operator (LASSO)-Cox regression. Subsequently, the prognostic potential of this model was evaluated using ROC (receiver operating characteristic) curve analysis, Kaplan-Meier survival curve analysis and decision curve analysis (DCA).</p><p><strong>Results: </strong>LECs exhibited association with angiogenesis, immune cell infiltration, immune escape, and epithelial-mesenchymal transition (EMT). Utilizing an 18-gene signature, gastric cancer patients from TCGA and GEO cohorts were stratified into high- risk and low-risk groups, with the former showing significantly poorer overall survival. Leveraging this gene signature, we designed a LECs-related gastric cancer prognostic model, demonstrating superior performance indicated by the area under the ROC curve (AUC) compared to existing models. Moreover, the nomogram and DCA underscored the clinical utility of our model in predicting the prognosis of GC patients.</p><p><strong>Conclusions: </strong>Our prognostic signature, based on 18 LECs-related genes, holds promise for refining overall survival prediction in gastric cancer patients, offering a valuable tool for clinical decision-making.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":11237,"journal":{"name":"Diagnostic Pathology","volume":"20 1","pages":"103"},"PeriodicalIF":2.3000,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12418689/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diagnostic Pathology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13000-025-01683-6","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PATHOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Gastric cancer is one of the most common cancers worldwide, with its prognosis influenced by factors such as tumor clinical stage, histological type, and the patient's overall health. Recent studies highlight the critical role of lymphatic endothelial cells (LECs) in the tumor microenvironment. Perturbations in LEC function in gastric cancer, marked by aberrant activation or damage, disrupt lymphatic fluid dynamics and impede immune cell infiltration, thereby modulating tumor progression and patient prognosis. Hence, we aimed to construct a prognostically discriminative model group in LECs-related factors.
Methods: Gene expression and clinical data of gastric cancer patients were obtained from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Fudan University Shanghai Cancer Center (FUSCC). Using the Wilcoxon test, we assessed the relationship between LECs, angiogenesis, and the immunological milieu. Differentially expressed and prognostically significant LEC-associated genes were identified through "limma" R package-assisted analysis coupled with univariate Cox analysis. A prognostic model was developed, and LEC-associated gene signatures were refined through least absolute shrinkage and selection operator (LASSO)-Cox regression. Subsequently, the prognostic potential of this model was evaluated using ROC (receiver operating characteristic) curve analysis, Kaplan-Meier survival curve analysis and decision curve analysis (DCA).
Results: LECs exhibited association with angiogenesis, immune cell infiltration, immune escape, and epithelial-mesenchymal transition (EMT). Utilizing an 18-gene signature, gastric cancer patients from TCGA and GEO cohorts were stratified into high- risk and low-risk groups, with the former showing significantly poorer overall survival. Leveraging this gene signature, we designed a LECs-related gastric cancer prognostic model, demonstrating superior performance indicated by the area under the ROC curve (AUC) compared to existing models. Moreover, the nomogram and DCA underscored the clinical utility of our model in predicting the prognosis of GC patients.
Conclusions: Our prognostic signature, based on 18 LECs-related genes, holds promise for refining overall survival prediction in gastric cancer patients, offering a valuable tool for clinical decision-making.
期刊介绍：
Diagnostic Pathology is an open access, peer-reviewed, online journal that considers research in surgical and clinical pathology, immunology, and biology, with a special focus on cutting-edge approaches in diagnostic pathology and tissue-based therapy. The journal covers all aspects of surgical pathology, including classic diagnostic pathology, prognosis-related diagnosis (tumor stages, prognosis markers, such as MIB-percentage, hormone receptors, etc.), and therapy-related findings. The journal also focuses on the technological aspects of pathology, including molecular biology techniques, morphometry aspects (stereology, DNA analysis, syntactic structure analysis), communication aspects (telecommunication, virtual microscopy, virtual pathology institutions, etc.), and electronic education and quality assurance (for example interactive publication, on-line references with automated updating, etc.).
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