ArticleTumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine2016
Downregulation of betaine homocysteine methyltransferase (BHMT) in hepatocellular carcinoma associates with poor prognosis.
Article in Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- Association between malnutrition and hyperhomocysteine in Alzheimer's disease patients and diet intervention of betaine.Journal of clinical laboratory analysis · 2017Trial
- Paradoxical oncogenic effects of hepatic Brca1 through modulating Bhmt.Scientific reports · 2026Article
- Betaine-homocysteine methyltransferase protects against acetaminophen-induced acute liver failure via BACH1-SCD1-oleic acid axis.Acta pharmacologica Sinica · 2026Article
- AMPK-Dependent Epigenetic Regulation of Metabolism Mediates the Anti-Cancer Action of Pterostilbene in Hepatocellular Carcinoma.Molecular nutrition & food research · 2025Article
- New insights into methionine's role in maintaining intestinal stem cell regeneration via autophagy regulation.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2025Review
- Identification of methionine metabolism related prognostic model and tumor suppressive functions of BHMT in hepatocellular carcinoma.Scientific reports · 2025Article
- Tumour heterogeneity and personalized treatment screening based on single-cell transcriptomics.Computational and structural biotechnology journal · 2025Article
- Integration of epigenomic and transcriptomic profiling uncovers EZH2 target genes linked to cysteine metabolism in hepatocellular carcinoma.Cell death & disease · 2024Article
- GATA4 downregulation enhances CCL20-mediated immunosuppression in hepatocellular carcinoma.Hepatology communications · 2024Article
- Effects of essential oil of Origanum onites and its major component carvacrol on the expression of toxicity pathway genes in HepG2 cells.BMC complementary medicine and therapies · 2024Article
- Dietary methionine restriction in cancer development and antitumor immunity.Trends in endocrinology and metabolism: TEM · 2024Review
- Identification and validation of key miRNAs and a microRNA-mRNA regulatory network associated with liver cancer.Cell cycle (Georgetown, Tex.) · 2024Article
- Epigenetic aberrations of gene expression in a rat model of hepatocellular carcinoma.Epigenetics · 2022Article
- HNF4α regulates sulfur amino acid metabolism and confers sensitivity to methionine restriction in liver cancer.Nature communications · 2020Article
- Large-Scale Differential Gene Expression Transcriptomic Analysis Identifies a Metabolic Signature Shared by All Cancer Cells.Biomolecules · 2020Article
- Identification and validation of a ten-gene set variation score as a diagnostic and prognostic stratification tool in hepatocellular carcinoma.American journal of translational research · 2020Article
- Serum choline is associated with hepatocellular carcinoma survival: a prospective cohort study.Nutrition & metabolism · 2020Article
- Application of the Transcriptional Disease Signature (TDSs) to Screen Melanoma-Effective Compounds in a Small Fish Model.Scientific reports · 2019Article
- Propranolol exhibits activity against hemangiomas independent of beta blockade.NPJ precision oncology · 2019Article
- Differential Proteomic Analysis of Hepatocellular Carcinomas fromCancer genomics & proteomicsArticle
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Betaine homocysteine methyltransferase (BHMT) catalyzes the synthesis of methionine using betaine and homocysteine (Hcy), which is restricted to the liver and kidney. Impaired BHMT pathway has been associated with hepatocellular carcinogenesis in Bhmt-/- mice model, and decreased BHMT was observed in a small sample of human hepatocellular carcinoma (HCC) patients. However, the prognostic significance of BHMT in HCC has not been elucidated. This study aimed to examine the expression of BHMT in HCC and investigate the relationship between its expression and prognosis of HCC patients. BHMT expression was analyzed in 68 paired HCC samples (HCC tissues vs matched adjacent non-cancerous liver tissues), 115 paraffin-embedded HCC sections (primary cohort), and 65 paraffin-embedded HCC sections (validation cohort) using immunohistochemistry (IHC). The results of IHC analysis showed that BHMT was decreased in tumorous tissues in 85.2 % (58/68) of cases compared to the corresponding adjacent non-tumorous liver tissues. Further correlation analyses indicated that the decreased BHMT expression was closely correlated with serum α-fetoprotein (AFP) (p = 0.011), tumor size (p = 0.039), and vascular invasion (p = 0.017). Moreover, HCC patients with low BHMT expression had shorter overall survival (OS) and time to recurrence (TTR) than those with high BHMT expression in both primary cohort (p < 0.0001) and validation cohort (p < 0.05) assessed by the Kaplan-Meier method. In addition, multivariate analysis showed that BHMT was an independent prognostic factor for OS and TTR in the two cohorts (all p < 0.005). Collectively, our study demonstrated that BHMT could be served as a potential prognostic marker for HCC patients.
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