ArticleInternational journal of biological sciences2024
Multi-Omics profiling identifies aldehyde dehydrogenase 2 as a critical mediator in the crosstalk between Treg-mediated immunosuppression microenvironment and hepatocellular carcinoma.
Article in International journal of biological sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Targeting ALDH2 with Alda-1 to reverse cisplatin resistance in lung adenocarcinoma.Cancer chemotherapy and pharmacology · 2026Article
- Kynurenine metabolism-related gene signature for prognostic stratification in hepatocellular carcinoma.Translational cancer research · 2026Article
- Gut microbiota and renal fibrosis: novel mechanistic insights and therapeutic potential.Acta pharmacologica Sinica · 2026Review
- ALDH2 inhibits FASN stabilization via the E3 ligase CBL to suppress lipid accumulation and liver cancer development.Biology direct · 2026Article
- ALDH2 inhibits head and neck tumorigenesis through RAS signaling suppression, transactivation of TGM2, and synergy with ALDH6A1.Cellular and molecular life sciences : CMLS · 2026Article
- Hepatitis B virus, alcohol, and liver cancer.Frontiers in oncology · 2026Review
- Dihydromyricetin Remodels the Tumor Immune Microenvironment in Hepatocellular Carcinoma: Development and Validation of a Prognostic Model.Current issues in molecular biology · 2025Article
- Advancing precision medicine in hepatocellular carcinoma: current challenges and future directions in liquid biopsy, immune microenvironment, single nucleotide polymorphisms, and conversion therapy.Hepatic oncology · 2025Review
- Recent updates and future perspectives about ALDH1B1 as a potential anticancer target: a review.Journal of cancer research and clinical oncology · 2025Review
- Decision-Making Biomarkers Guiding Therapeutic Strategies in Hepatocellular Carcinoma: From Prediction to Personalized Care.Cancers · 2025Review
- Genetic Polymorphisms ofInternational journal of molecular sciences · 2025Review
- Atlas of lysine propionylation of human right atrium and ALDH6A1-NADH pathway in new-onset atrial fibrillation after coronary surgery.Communications biology · 2025Article
- Alcohol-Metabolizing Enzymes, Liver Diseases and Cancer.Seminars in liver disease · 2025Review
- Leveraging Single-Cell Multi-Omics to Decode Tumor Microenvironment Diversity and Therapeutic Resistance.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Identifying metabolism-related genes in liver cancer through weighted gene co-expression network analysis and machine learning.Frontiers in genetics · 2025Article
- CD4Trends in cancer · 2024Review
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Authors and funding
16 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dysregulation of the aldehyde dehydrogenase (ALDH) family has been implicated in various pathological conditions, including cancer. However, a systematic evaluation of ALDH alterations and their therapeutic relevance in hepatocellular carcinoma (HCC) remains lacking. Herein, we found that 15 of 19 ALDHs were transcriptionally dysregulated in HCC tissues compared to normal liver tissues. A four gene signature, including ALDH2, ALDH5A1, ALDH6A1, and ALDH8A1, robustly predicted prognosis and defined a high-risk subgroup exhibiting immunosuppressive features like regulatory T cell (Tregs) infiltration. Single-cell profiling revealed selective overexpression of tumor necrosis factor receptor superfamily member 18 (TNFRSF18) on Tregs, upregulated in high-risk HCC patients. We identified ALDH2 as a tumor suppressor in HCC, with three novel phosphorylation sites mediated by protein kinase C zeta that enhanced enzymatic activity. Mechanistically, ALDH2 suppressed Tregs differentiation by inhibiting β-catenin/TGF-β1 signaling in HCC. Collectively, our integrated multi-omics analysis defines an ALDH-Tregs-TNFRSF18 axis that contributes to HCC pathogenesis and represents potential therapeutic targets for this aggressive malignancy.
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