Loading
Life sciences · Journal article
Cancer Biology & Therapy · September 21, 2026
No summary has been generated for this record yet. What follows is drawn from its source metadata only.
Journal article.
No findings were extractable from the material analysed.
Safety was not reported in the material analysed. Check the source before drawing any conclusion about harm.
The source did not state who this applies to in practice.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
This record has not been graded across any dimension yet. Treat the label above as provisional and read the source.
What is missing. This record has no bottom line, key findings, reported figures, evidence dimensions. That is a gap in the analysis, not a judgement about the study.
Intrahepatic cholangiocarcinoma (ICC) is an aggressive liver malignancy with heterogeneous responses to gemcitabine-based chemotherapy. The cellular and microenvironmental programs associated with the gemcitabine response remain incompletely understood. This study aimed to identify tumor microenvironment-associated regulators of gemcitabine response in ICC and evaluate their functional relevance using patient-derived organoids. Four public single-cell RNA sequencing datasets comprising 50,176 cells were integrated with TCGA-based transcriptomic and drug sensitivity analyses. High-dimensional weighted gene co-expression network analysis was used to identify cell type-associated modules. Predicted gemcitabine IC50-related differentially expressed genes were intersected with the fibroblast-associated module genes. Patient-derived ICC organoids were used for gemcitabine sensitivity testing and CRISPR/Cas9-mediated TPM2 knockout validation. Single-cell analysis revealed fibroblast enrichment in ICC, and co-expression analysis identified fibroblast-associated modules enriched in extracellular matrix organization and ECM-receptor interaction. Integrated analysis identified TPM2 as a fibroblast-enriched candidate associated with poor prognosis, activation of epithelial-mesenchymal transition, TGF-β and Notch-related pathways, and dynamic cellular state transitions. Patient-derived ICC organoids retained features of matched tumors and showed distinct gemcitabine sensitivities that were broadly consistent with the clinical imaging responses. In a relatively gemcitabine-resistant organoid model, TPM2 knockout enhanced gemcitabine-induced cytotoxicity and suppressed EMT/ECM-related programs and Notch signaling. These findings identify TPM2-associated cell-matrix remodeling as a potential contributor to gemcitabine resistance in ICC and support patient-derived organoids as a functional platform for studying therapeutic vulnerabilities.