ArticlePloS one2014
Biomarkers of TGF-β signaling pathway and prognosis of pancreatic cancer.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 2 of them syntheses that pooled it.
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Who cites it
71 citing papers in PubMed, 2 syntheses or guidelines pooled it, 137 citations in OpenAlex.
- Clinicopathological significance of SMAD4 loss in pancreatic ductal adenocarcinomas: a systematic review and meta-analysis.Oncotarget · 2017Pooled it
- Meta-analysis of the prognostic value of smad4 immunohistochemistry in various cancers.PloS one · 2014Pooled it
- HNRNPF Increases MAF and CCNB2 Levels To Promote Cancer Cell Stemness and Progression of Pancreatic Ductal Adenocarcinoma.Stem cell reviews and reports · 2026Article
- The TGF-βR1 inhibitor galunisertib re-shapes the PDAC-TME by limiting decidual-like natural killer cells polarization.Cell death & disease · 2026Article
- Article
- TGFB2 Expression and Methylation Predict Overall Survival in Pancreatic Ductal Adenocarcinoma Patients.International journal of molecular sciences · 2025Article
- RGS3 acts as a tumor promoter by facilitating the regulation of the TGF-β signaling pathway and promoting EMT in ovarian cancer.Cell death discovery · 2025Article
- Exploring the Role of the TGF-β Signaling Pathway in Colorectal Precancerous Polyps Biochemical Genetics.Biochemical genetics · 2025Review
- Extracellular Vesicles Secreted by Cancer-Associated Fibroblasts Drive Non-Invasive Cancer Cell Progression to Metastasis via TGF-β Signalling Hyperactivation.Journal of extracellular vesicles · 2025Article
- The Oncoprotein Mucin 1 in Pancreatic Cancer Onset and Progression: Potential Clinical Implications.Biomolecules · 2025Review
- HPK1 Dysregulation-Associated NK Cell Dysfunction and Defective Expansion Promotes Metastatic Melanoma Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Unraveling the interplay: exploring signaling pathways in pancreatic cancer in the context of pancreatic embryogenesis.Frontiers in cell and developmental biology · 2024Review
- Simultaneously targeting extracellular vesicle trafficking and TGF-β receptor kinase activity blocks signaling hyperactivation and metastasis.Signal transduction and targeted therapy · 2023Article
- Effect of chimeric antigen receptor T cells against protease-activated receptor 1 for treating pancreatic cancer.BMC medicine · 2023Article
- Significance of Lipopolysaccharides in Gastric Cancer and Their Potential as a Biomarker for Nivolumab Sensitivity.International journal of molecular sciences · 2023Article
- Horizontal Transfer of Malignant Traits and the Involvement of Extracellular Vesicles in Metastasis.Cells · 2023Review
- Proinflammatory plasticity towards Th17 paradigm of regulatory T cells consistent with elevated prevalence of TGFBR2 variants in elderly patients with primary immune thrombocytopenia.BMC immunology · 2023Article
- TFG-β Nuclear Staining as a Potential Relapse Risk Factor in Early-Stage Non-Small-Cell Lung Cancer.International journal of molecular sciences · 2022Article
- Systems biology and OMIC data integration to understand gastrointestinal cancers.World journal of clinical oncology · 2022Review
- Signaling pathways and therapeutic interventions in gastric cancer.Signal transduction and targeted therapy · 2022Review
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundTransforming growth factor (TGF)-β signaling pathway, may act both as a tumor suppressor and as a tumor promoter in pancreatic cancer, depending on tumor stage and cellular context. TGF-β pathway has been under intensive investigation as a potential therapeutic target in the treatment of cancer. We hypothesized a correlation between TGF-βR2/SMAD4 expression in the tumor, plasma TGF-β1 ligand level, genetic variation in TGF-B pathway and prognosis of pancreatic cancer.
methodWe examined TGF-βR2 and SMAD4 protein expression in biopsy or surgical samples from 91 patients with pancreatic ductal adenocarcinoma (PDAC) using immunohistochemistry. Plasma level of TGF-β1 was measured in 644 patients with PDAC using ELISA. Twenty-eight single nucleotide polymorphisms (SNP) of the TGF-β1, TGF-β2, TGF-β3, TGF-βR1, TGF-βR2, and SMAD4 genes were determined in 1636 patients with PDAC using the Sequenom method. Correlation between protein expression in the tumor, plasma TGF-β1 level, and genotypes with overall survival (OS) was evaluated with Cox proportional regression models.
resultsThe expression level of TGF-βR2 and SMAD4 as an independent marker was not associated with OS. However, patients with both low nuclear staining of TGF-βR2 and high nuclear staining of SMAD4 may have better survival (P = 0.06). The mean and median level of TGF-β1 was 15.44 (SD: 10.99) and 12.61 (interquartile range: 8.31 to 19.04) ng/ml respectively. Patients with advanced disease and in the upper quartile range of TGF-β1 level had significantly reduced survival than those with low levels (P = 0.02). A significant association of SMAD4 SNP rs113545983 with overall survival was observed (P<0.0001).
conclusionOur data provides valuable baseline information regarding the TGF-β pathway in pancreatic cancer, which can be utilized in targeted therapy clinical trials. High TGF-β1 plasma level, SMAD4 SNP or TGF-βR2/SMAD4 tumor protein expression may suggest a dependence on this pathway in patients with advanced pancreatic cancer.
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