ArticleExperimental & molecular medicine2023
Clinical molecular subtyping reveals intrinsic mesenchymal reprogramming in gastric cancer cells.
Article in Experimental & molecular medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Review
- The "Hit-and-Run" legacy: epigenetic locking and the survival switch in H. pylori-associated gastric cancer.Cell death discovery · 2026Review
- Review
- The tumor microenvironment shapes gastric cancer progression by coordinating immune suppression and metabolic reprogramming.Frontiers in immunology · 2026Review
- Spatially resolved endothelial signaling via nampt-itga5 drives immune evasion in stem-like gastric cancer.Cancer immunology, immunotherapy : CII · 2025Article
- Blood TCTP as a potential biomarker associated with immunosuppressive features and poor clinical outcomes in metastatic gastric cancer.Journal for immunotherapy of cancer · 2025Article
- Application of Spatial Transcriptomics in Digestive System Tumors.Biomolecules · 2024Review
- Single-cell RNA sequencing to map tumor heterogeneity in gastric carcinogenesis paving roads to individualized therapy.Cancer immunology, immunotherapy : CII · 2024Review
- IFIT1 + neutrophil is a causative factor of immunosuppressive features of poorly cohesive carcinoma (PCC).Journal of translational medicine · 2024Article
- Spatial transcriptomics in cancer research and potential clinical impact: a narrative review.Journal of cancer research and clinical oncology · 2024Review
- Whole-transcriptome sequencing in advanced gastric or gastroesophageal cancer: A deep dive into its clinical potential.Cancer science · 2024Article
- Exploring the current landscape of single-cell RNA sequencing applications in gastric cancer research.Journal of cellular and molecular medicine · 2024Review
- Review
Corrections and comments
- Erratum issued
Authors and funding
17 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mesenchymal cancer phenotype is known to be clinically related to treatment resistance and a poor prognosis. We identified gene signature-based molecular subtypes of gastric cancer (GC, n = 547) based on transcriptome data and validated their prognostic and predictive utility in multiple external cohorts. We subsequently examined their associations with tumor microenvironment (TME) features by employing cellular deconvolution methods and sequencing isolated GC populations. We further performed spatial transcriptomics analysis and immunohistochemistry, demonstrating the presence of GC cells in a partial epithelial-mesenchymal transition state. We performed network and pharmacogenomic database analyses to identify TGF-β signaling as a driver pathway and, thus, a therapeutic target. We further validated its expression in tumor cells in preclinical models and a single-cell dataset. Finally, we demonstrated that inhibition of TGF-β signaling negated mesenchymal/stem-like behavior and therapy resistance in GC cell lines and mouse xenograft models. In summary, we show that the mesenchymal GC phenotype could be driven by epithelial cancer cell-intrinsic TGF-β signaling and propose therapeutic strategies based on targeting the tumor-intrinsic mesenchymal reprogramming of medically intractable GC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.