ArticleStem cell research & therapy2022
A gene signature is critical for intrahepatic cholangiocarcinoma stem cell self-renewal and chemotherapeutic response.
Article in Stem cell research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 15 citations in OpenAlex.
- Role of methionine metabolism in cancer: recent advances in molecular mechanisms and therapeutic implications.Experimental hematology & oncology · 2026Review
- How to efficiently establish animal models of cholangiocarcinoma: challenges and inspiration.Medical review (2021) · 2026Review
- Methionine restriction for cancer therapy: From preclinical studies to clinical trials.Cancer pathogenesis and therapy · 2026Review
- Amino acid metabolic reprogramming: future prospects for cholangiocarcinoma therapy.Cell death discovery · 2026Review
- Methionine restriction in cancer: a dietary insight for therapy.Frontiers in nutrition · 2026Review
- Tumor-associated neutrophils drive liver-specific metastatic progression in breast cancer through methionine metabolism mediated by methionine adenosyltransferase II alpha.Translational cancer research · 2025Article
- Transcriptome-based molecular subgroup identification and prognosis stratification in pediatric AML.Annals of hematology · 2025Article
- Investigating combined hypoxia and stemness indices for prognostic transcripts in gastric cancer: Machine learning and network analysis approaches.Biochemistry and biophysics reports · 2025Article
- Mitochondrial Ribosomal Proteins and Cancer.Medicina (Kaunas, Lithuania) · 2025Review
- Applications of 3D models in cholangiocarcinoma.Frontiers in oncology · 2025Review
- DrugFormer: Graph-Enhanced Language Model to Predict Drug Sensitivity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Research progress and prospect of postoperative adjuvant therapy for resectable intrahepatic cholangiocarcinoma.Frontiers in pharmacology · 2024Review
- Stemness of Normal and Cancer Cells: The Influence of Methionine Needs and SIRT1/PGC-1α/PPAR-α Players.Cells · 2022Review
- Characterization of cellular senescence patterns predicts the prognosis and therapeutic response of hepatocellular carcinoma.Frontiers in molecular biosciences · 2022Article
- Identifying enhancer-driven subtype-specific prognostic markers in breast cancer based on multi-omics data.Frontiers in immunology · 2022Article
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10 authors at 4 institutions in 1 country.
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Abstract
backgroundImproved understanding of the stemness regulation mechanism in intrahepatic cholangiocarcinoma (ICC) could identify targets and guidance for adjuvant transarterial chemoembolization (TACE).
methodsTCGA database was excavated to identify the ICC stemness-associated genes. The pro-stemness effect of target genes was further analyzed by sphere formation assay, qRT-PCR, western blot, flow cytometric analysis, IHC, CCK8 assay and metabolomic analysis. Based on multivariate analysis, a nomogram for ICC patients with adjuvant TACE was established and our result was further confirmed by a validation cohort. Finally, the effect of dietary methionine intervention on chemotherapy was estimated by in vivo experiment and clinical data.
resultsIn this study, we identified four ICC stemness-associated genes (SDHAF2, MRPS34, MRPL11, and COX8A) that are significantly upregulated in ICC tissues and negatively associated with clinical outcome. Functional studies indicated that these 4-key-genes are associated with self-renewal ability of ICC and transgenic expression of these 4-key-genes could enhance chemoresistance of cholangiocarcinoma cells. Mechanistically, the 4-key-genes-mediated pro-stemness requires the activation of methionine cycle, and their promotion on ICC stemness characteristic is dependent on MAT2A. Importantly, we established a novel nomogram to evaluate the effectiveness of TACE for ICC patients. Further dietary methionine intervene studies indicated that patients with adjuvant TACE might benefit from dietary methionine restriction if they have a relatively high nomogram score (≥ 135).
conclusionsOur results show that four ICC stemness-associated genes could serve as novel biomarkers in predicting ICC patient's response to adjuvant TACE and their pro-stemness ability may be attributed to the activation of the methionine cycle.
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