ArticleBreast cancer research : BCR2019
Epigenetic silencing of TGFBI confers resistance to trastuzumab in human breast cancer.
Article in Breast cancer research : BCR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 71 citations in OpenAlex.
- miR-770-5p regulates KDM5B and links its nuclear localization to HER2 signaling in trastuzumab-resistant breast cancer.Molecular and cellular biochemistry · 2026Article
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- The Great Potential of DNA Methylation in Triple-Negative Breast Cancer: From Biological Basics to Clinical Application.Biomedicines · 2026Review
- Epigenetic modifications in ferroptosis regulation of breast cancer.American journal of cancer research · 2026Review
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- HER2-Positive Breast Cancer-Current Treatment Management and New Therapeutic Methods for Brain Metastasis.Biomedicines · 2025Review
- Decoding the Epigenome of Breast Cancer.International journal of molecular sciences · 2025Review
- GluOC Induced SLC7A11 and SLC38A1 to Activate Redox Processes and Resist Ferroptosis in TNBC.Cancers · 2025Article
- Role of exosomes in transforming growth factor-β-mediated cancer cell plasticity and drug resistance.Exploration of targeted anti-tumor therapy · 2025Review
- Decoding breast cancer treatment resistance through genetic, epigenetic, and immune-regulatory mechanisms: from molecular insights to translational perspectives.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Analysis of methylation features associated with neoadjuvant efficacy in HER2-positive breast cancer.Frontiers in oncology · 2025Article
- Discovery of drug transporter inhibitors tied to long noncoding RNA in resistant cancer cells; a computational model -in silico- study.Frontiers in immunology · 2025Review
- Article
- Targeted Sequencing of HER2-Positive Breast Cancer Mutations Revealed a Potential Association between PIK3CA and Trastuzumab Resistance.Asian Pacific journal of cancer prevention : APJCP · 2024Article
- Targeting SMAD3 Improves Response to Oxaliplatin in Esophageal Adenocarcinoma Models by Impeding DNA Repair.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Transforming growth factor-induced gene TGFBI is correlated with the prognosis and immune infiltrations of breast cancer.World journal of surgical oncology · 2024Article
- Sparse spectral graph analysis and its application to gastric cancer drug resistance-specific molecular interplays identification.PloS one · 2024Article
- 5-Aza-2'-Deoxycytidine Alters the Methylation Profile of Bortezomib-Resistant U266 Multiple Myeloma Cells and Affects Their Proliferative Potential.International journal of molecular sciences · 2023Article
- Breast Cancer Chemoresistance: Insights into the Regulatory Role of lncRNA.International journal of molecular sciences · 2023Review
- Integrative analysis reveals that SLC38A1 promotes hepatocellular carcinoma development via PI3K/AKT/mTOR signaling via glutamine mediated energy metabolism.Journal of cancer research and clinical oncology · 2023Article
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Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
Abstract
backgroundAcquired resistance to trastuzumab is a major clinical problem in the treatment of HER2-positive (HER2+) breast cancer patients. The selection of trastuzumab-resistant patients is a great challenge of precision oncology. The aim of this study was to identify novel epigenetic biomarkers associated to trastuzumab resistance in HER2+ BC patients.
methodsWe performed a genome-wide DNA methylation (450K array) and a transcriptomic analysis (RNA-Seq) comparing trastuzumab-sensitive (SK) and trastuzumab-resistant (SKTR) HER2+ human breast cancer cell models. The methylation and expression levels of candidate genes were validated by bisulfite pyrosequencing and qRT-PCR, respectively. Functional assays were conducted in the SK and SKTR models by gene silencing and overexpression. Methylation analysis in 24 HER2+ human BC samples with complete response or non-response to trastuzumab-based treatment was conducted by bisulfite pyrosequencing.
resultsEpigenomic and transcriptomic analysis revealed the consistent hypermethylation and downregulation of TGFBI, CXCL2, and SLC38A1 genes in association with trastuzumab resistance. The DNA methylation and expression levels of these genes were validated in both sensitive and resistant models analyzed. Of the genes, TGFBI presented the highest hypermethylation-associated silencing both at the transcriptional and protein level. Ectopic expression of TGFBI in the SKTR model suggest an increased sensitivity to trastuzumab treatment. In primary tumors, TGFBI hypermethylation was significantly associated with trastuzumab resistance in HER2+ breast cancer patients.
conclusionsOur results suggest for the first time an association between the epigenetic silencing of TGFBI by DNA methylation and trastuzumab resistance in HER2+ cell models. These results provide the basis for further clinical studies to validate the hypermethylation of TGFBI promoter as a biomarker of trastuzumab resistance in HER2+ breast cancer patients.
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