ArticleCell death & disease2017
NGS-based transcriptome profiling reveals biomarkers for companion diagnostics of the TGF-β receptor blocker galunisertib in HCC.
Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 52 citations in OpenAlex.
- WWP1 gain-of-function drives developmental anoikis through TGFβ pathway during neurodevelopment.Cell death discovery · 2026Article
- Companion Diagnostics in Clinical Therapy: Current Applications and Future Directions.MedComm · 2026Review
- TGF-β in tumor development and progression: mechanisms and therapeutics.Molecular biomedicine · 2026Review
- Spatial Transcriptomics and snRNA-seq Expose CAF Niches Orchestrating Dual Stromal-Immune Barriers in Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- A prognostic model of 8-T/B cell receptor-related signatures for hepatocellular carcinoma.Discover oncology · 2025Article
- mAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- GPR56 facilitates hepatocellular carcinoma metastasis by promoting the TGF-β signaling pathway.Cell death & disease · 2024Article
- Transcriptomic evidence for tumor-specific beneficial or adverse effects of TGFβ pathway inhibition on the prognosis of patients with liver cancer.FEBS open bio · 2023Article
- Deciphering the role of transforming growth factor-beta 1 as a diagnostic-prognostic-therapeutic candidate against hepatocellular carcinoma.World journal of gastroenterology · 2022Review
- Small Molecule Inhibitors for Hepatocellular Carcinoma: Advances and Challenges.Molecules (Basel, Switzerland) · 2022Review
- Transforming growth factor β latency: A mechanism of cytokine storage and signalling regulation in liver homeostasis and disease.JHEP reports : innovation in hepatology · 2022Review
- Chemotherapeutic Drug-Regulated Cytokines Might Influence Therapeutic Efficacy in HCC.International journal of molecular sciences · 2021Review
- Improving function of cytotoxic T-lymphocytes by transforming growth factor-β inhibitor in oral squamous cell carcinoma.Cancer science · 2021Article
- Review
- Distinct functions of transforming growth factor-β signaling in c-MYC driven hepatocellular carcinoma initiation and progression.Cell death & disease · 2021Article
- Targeting TGFβ signal transduction for cancer therapy.Signal transduction and targeted therapy · 2021Review
- Identification of Gene-Set Signature in Early-Stage Hepatocellular Carcinoma and Relevant Immune Characteristics.Frontiers in oncology · 2021Article
- The Influence of Adalimumab and Cyclosporine A on the Expression Profile of the Genes Related to TGFMediators of inflammation · 2020Article
- Validation of Hepatocellular Carcinoma Experimental Models for TGF-β Promoting Tumor Progression.Cancers · 2019Review
- PMEPA1 induces EMT via a non-canonical TGF-β signalling in colorectal cancer.Journal of cellular and molecular medicine · 2019Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transforming growth factor-beta (TGF-β) signaling has gained extensive interest in hepatocellular carcinoma (HCC). The small molecule kinase inhibitor galunisertib, targeting the TGF-β receptor I (TGF-βRI), blocks HCC progression in preclinical models and shows promising effects in ongoing clinical trials. As the drug is not similarly effective in all patients, this study was aimed at identifying new companion diagnostics biomarkers for patient stratification. Next-generation sequencing-based massive analysis of cDNA ends was used to investigate the transcriptome of an invasive HCC cell line responses to TGF-β1 and galunisertib. These identified mRNA were validated in 78 frozen HCC samples and in 26 ex-vivo HCC tissues treated in culture with galunisertib. Respective protein levels in patients blood were measured by enzyme-linked immunosorbent assay. SKIL, PMEPA1 ANGPTL4, SNAI1, Il11 and c4orf26 were strongly upregulated by TGF-β1 and downregulated by galunisertib in different HCC cell lines. In the 78 HCC samples, only SKIL and PMEPA1 (P<0.001) were correlated with endogenous TGF-β1. In ex-vivo samples, SKIL and PMEPA1 were strongly downregulated (P<0.001), and correlated (P<0.001) with endogenous TGF-β1. SKIL and PMEPA1 mRNA expression in tumor tissues was significantly increased compared with controls and not correlated with protein levels in the blood of paired HCC patients. SKIL and PMEPA1 mRNA levels were positively correlated with TGF-β1 mRNA concentrations in HCC tissues and strongly downregulated by galunisertib. The target genes identified here may serve as biomarkers for the stratification of HCC patients undergoing treatment with galunisertib.
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