Single-cell transcriptomic mapping of patient-derived primary liver cancer organoids reveals molecular subtypes and guides precision drug targeting.
1/5 보강
[BACKGROUND] Current liver cancer research lacks reliable in vitro models that replicate tumor pathophysiology.
APA
Dai S, Wu J, et al. (2026). Single-cell transcriptomic mapping of patient-derived primary liver cancer organoids reveals molecular subtypes and guides precision drug targeting.. Cellular oncology (Dordrecht, Netherlands), 49(2). https://doi.org/10.1007/s13402-026-01190-w
MLA
Dai S, et al.. "Single-cell transcriptomic mapping of patient-derived primary liver cancer organoids reveals molecular subtypes and guides precision drug targeting.." Cellular oncology (Dordrecht, Netherlands), vol. 49, no. 2, 2026.
PMID
41838232 ↗
Abstract 한글 요약
[BACKGROUND] Current liver cancer research lacks reliable in vitro models that replicate tumor pathophysiology. This study establishes primary liver cancer (PLC) organoids from three major subtypes—hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and combined hepatocellular-cholangiocarcinoma (CHC)—to enable precise diagnostics and personalized therapies through comprehensive genomic profiling.
[METHODS] Organoid cultures were generated from 11 PLC patients (5 HCC, 3 ICC, 3 CHC). Whole exome sequencing (WES), RNA-seq, and single-cell RNA-seq (scRNA-seq) were performed to analyze molecular differences. Drug screening targeting subtype-specific pathways was conducted to validate sequencing findings.
[RESULTS] WES and RNA-seq confirmed that organoids retained parental tumor genetics and heterogeneity, distinct from paracancerous tissues. scRNA-seq revealed distinct cell populations in HCC, ICC, and CHC organoids. Lipid metabolism was enriched in HCC organoids; tumor migration pathways were upregulated in ICC organoids; and mitochondrial function was enhanced in CHC organoids. Rosuvastatin inhibited HCC growth by targeting lipid metabolism, while pemigatinib reduced ICC malignancy by suppressing epithelial-mesenchymal transition. Regorafenib impaired mitochondrial function in CHC organoids, slowing progression.
[CONCLUSIONS] PLC-derived organoids serve as robust tools for biomarker discovery and drug screening. scRNA-seq elucidates inter- and intra-tumoral heterogeneity, offering insights for precision therapy in liver cancer. This model advances personalized treatment strategies for diverse PLC subtypes.
[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1007/s13402-026-01190-w.
[METHODS] Organoid cultures were generated from 11 PLC patients (5 HCC, 3 ICC, 3 CHC). Whole exome sequencing (WES), RNA-seq, and single-cell RNA-seq (scRNA-seq) were performed to analyze molecular differences. Drug screening targeting subtype-specific pathways was conducted to validate sequencing findings.
[RESULTS] WES and RNA-seq confirmed that organoids retained parental tumor genetics and heterogeneity, distinct from paracancerous tissues. scRNA-seq revealed distinct cell populations in HCC, ICC, and CHC organoids. Lipid metabolism was enriched in HCC organoids; tumor migration pathways were upregulated in ICC organoids; and mitochondrial function was enhanced in CHC organoids. Rosuvastatin inhibited HCC growth by targeting lipid metabolism, while pemigatinib reduced ICC malignancy by suppressing epithelial-mesenchymal transition. Regorafenib impaired mitochondrial function in CHC organoids, slowing progression.
[CONCLUSIONS] PLC-derived organoids serve as robust tools for biomarker discovery and drug screening. scRNA-seq elucidates inter- and intra-tumoral heterogeneity, offering insights for precision therapy in liver cancer. This model advances personalized treatment strategies for diverse PLC subtypes.
[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1007/s13402-026-01190-w.
🏷️ 키워드 / MeSH 📖 같은 키워드 OA만
같은 제1저자의 인용 많은 논문 (5)
- Metabolic dysregulation: Its role in diabetes mellitus and cancers.
- Effects of esketamine combined with QLB in older frail patients with colorectal cancer surgery.
- Systemic activation and tissue infiltration of CD8 + CX3CR1 + T cells in non-small cell lung cancer treated with neoadjuvant immune checkpoint blockade.
- The multidimensional roles and mechanisms of exercise intervention in pediatric oncology.
- Recent advances in the management of pancreatic neuroendocrine tumors: From diagnosis, treatment to biology.
🏷️ 같은 키워드 · 무료전문 — 이 논문 MeSH/keyword 기반
- Microfluidic-based patient-derived organoids recapitulate thyroid cancer heterogeneity and reveal NF-κB-driven maturation for precision therapy.
- Single-cell and spatial transcriptome analysis of breast cancer tumor-associated fibroblast heterogeneity and its mediated remodeling of the tumor microenvironment.
- Targeting Fatty Acids in Liver Cancer: Molecular Insights and Drug Approaches.
- Ferritin-based nanocarrier delivery of KRAS G12D inhibitor in pancreatic adenocarcinoma cells and patient-derived organoids: A novel approach for treatment.
- Rare fusion transcript in a refractory adult T-cell lymphoblastic lymphoma.
- Comprehensive Bioinformatics Analysis and Experimental Verification RNF186 Is a Recurrence Signature Gene of Hepatocellular Carcinoma that Promotes Cell Proliferation.