ArticleMolecular medicine (Cambridge, Mass.)2022
Hypermethylation of TMEM240 predicts poor hormone therapy response and disease progression in breast cancer.
Article in Molecular medicine (Cambridge, Mass.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 14 citations in OpenAlex.
- SFMBT2 hypermethylation promotes colorectal cancer progression and is a potential noninvasive biomarker for advanced CRC.iScience · 2026Article
- Monitoring breast cancer progression through circulating methylated GCM2 and TMEM240 detection.Clinical epigenetics · 2025Article
- [Neurospecific transmembrane protein 240 colocalizes with peroxisomes and activates Rho GDP dissociation inhibitor β].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Liquid Biopsy-Based DNA Methylation Biomarkers for Precision Medicine in Breast Cancer.Expert reviews in molecular medicine · 2025Review
- Liquid biopsies for early detection and monitoring of cancer: advances, challenges, and future directions.Annals of medicine and surgery (2012) · 2025Review
- Genome-wide methylation profiling of maternal cell-free DNA using methylated DNA sequencing (MeD-seq) indicates a placental and immune-cell signature.European journal of clinical investigation · 2025Article
- Hypermethylation of the Gene Body inBiomolecules · 2024Article
- Review
- Review
- Size and Methylation Index of Cell-Free and Cell-Surface-Bound DNA in Blood of Breast Cancer Patients in the Contest of Liquid Biopsy.International journal of molecular sciences · 2022Article
- Exosomes in Breast Cancer: Involvement in Tumor Dissemination and Prospects for Liquid Biopsy.International journal of molecular sciences · 2022Review
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundApproximately 25% of patients with early-stage breast cancer experience cancer progression throughout the disease course. Alterations in TMEM240 in breast cancer were identified and investigated to monitor treatment response and disease progression.
methodsCirculating methylated TMEM240 in the plasma of breast cancer patients was used to monitor treatment response and disease progression. The Cancer Genome Atlas (TCGA) data in Western countries and Illumina methylation arrays in Taiwanese breast cancer patients were used to identify novel hypermethylated CpG sites and genes related to poor hormone therapy response. Quantitative methylation-specific PCR (QMSP), real-time reverse transcription PCR, and immunohistochemical analyses were performed to measure DNA methylation and mRNA and protein expression levels in 394 samples from Taiwanese and Korean breast cancer patients. TMEM240 gene manipulation, viability, migration assays, RNA-seq, and MetaCore were performed to determine its biological functions and relationship to hormone drug treatment response in breast cancer cells.
resultsAberrant methylated TMEM240 was identified in breast cancer patients with poor hormone therapy response using genome-wide methylation analysis in the Taiwan and TCGA breast cancer cohorts. A cell model showed that TMEM240, which is localized to the cell membrane and cytoplasm, represses breast cancer cell proliferation and migration and regulates the expression levels of enzymes involved in estrone and estradiol metabolism. TMEM240 protein expression was observed in normal breast tissues but was not detected in 88.2% (67/76) of breast tumors and in 90.0% (9/10) of metastatic tumors from breast cancer patients. QMSP revealed that in 54.5% (55/101) of Taiwanese breast cancer patients, the methylation level of TMEM240 was at least twofold higher in tumor tissues than in matched normal breast tissues. Patients with hypermethylation of TMEM240 had poor 10-year overall survival (p = 0.003) and poor treatment response, especially hormone therapy response (p < 0.001). Circulating methylated TMEM240 dramatically and gradually decreased and then diminished in patients without disease progression, whereas it returned and its levels in plasma rose again in patients with disease progression. Prediction of disease progression based on circulating methylated TMEM240 was found to have 87.5% sensitivity, 93.1% specificity, and 90.2% accuracy.
conclusionsHypermethylation of TMEM240 is a potential biomarker for treatment response and disease progression monitoring in breast cancer.
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