ArticleCell death & disease2021
The distinct responsiveness of cytokeratin 19-positive hepatocellular carcinoma to regorafenib.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Diagnostic value of radiomics in predicting Ki-67 and cytokeratin 19 expression in hepatocellular carcinoma: a systematic review and meta-analysis.Frontiers in oncology · 2023Pooled it
- Review Article: Biomarkers in Liver Transplantation for Hepatocellular Carcinoma: Towards Precision Medicine.Alimentary pharmacology & therapeutics · 2026Review
- China Liver Cancer Guidelines for the Diagnosis and Treatment of Hepatocellular Carcinoma (2024 Edition).Liver cancer · 2025Article
- The latest progress of personalized drug screening and therapy research for common clinical tumors through the PDX model platform.Journal of pharmaceutical analysis · 2025Review
- An Update of Immunohistochemistry in Hepatocellular Carcinoma.Diagnostics (Basel, Switzerland) · 2025Review
- Development and validation of a combined radiomic and clinical model based on contrast-enhanced ultrasound for preoperative prediction of CK19-positive hepatocellular carcinoma.Abdominal radiology (New York) · 2025Article
- Patient-derived xenograft model: Applications and challenges in liver cancer.Chinese medical journal · 2025Review
- PDX models for functional precision oncology and discovery science.Nature reviews. Cancer · 2025Review
- MRI-based deep learning radiomics to differentiate dual-phenotype hepatocellular carcinoma from HCC and intrahepatic cholangiocarcinoma: a multicenter study.Insights into imaging · 2025Article
- Impact of Cytokeratin 19 Expression on the Outcomes of Unresectable Hepatocellular Carcinoma Treated with Targeted Therapy and Immunotherapy: A Propensity Score Matched Analysis.Journal of hepatocellular carcinoma · 2025Article
- Impact of immunosuppressants on tumor pulmonary metastasis: new insight into transplantation for hepatocellular carcinoma.Cancer biology & medicine · 2024Review
- Radiomics predicting immunohistochemical markers in primary hepatic carcinoma: Current status and challenges.Heliyon · 2024Review
- Prognostic implications of CK19 positivity in patients with early recurrent hepatocellular carcinoma after hepatic resection undergoing transarterial chemoembolization.BMC gastroenterology · 2024Article
- FGF21 modulates immunometabolic homeostasis via the ALOX15/15-HETE axis in early liver graft injury.Nature communications · 2024Article
- Lefamulin Overcomes Acquired Drug Resistance via Regulating Mitochondrial Homeostasis by Targeting ILF3 in Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Transcription factor 7 like 2 promotes metastasis in hepatocellular carcinoma via NEDD9-mediated activation of AKT/mTOR signaling pathway.Molecular medicine (Cambridge, Mass.) · 2024Article
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- Clonorchis sinensis infection amplifies hepatocellular carcinoma stemness, predicting unfavorable prognosis.PLoS neglected tropical diseases · 2024Article
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cytokeratin 19-positive (CK19+) hepatocellular carcinoma (HCC) is an aggressive subtype characterized by early recurrence and chemotherapy tolerance. However, there is no specific therapeutic option for CK19+ HCC. The correlation between tumor recurrence and expression status of CK19 were studied in 206 patients undergoing liver transplantation for HCC. CK19-/+ HCC cells were isolated to screen effective antitumor drugs. The therapeutic effects of regorafenib were evaluated in patient-derived xenograft (PDX) models from 10 HCC patients. The mechanism of regorafenib on CK19+ HCC was investigated. CK19 positiveness indicated aggressiveness of tumor and higher recurrence risk of HCC after liver transplantation. The isolated CK19+ HCC cells had more aggressive behaviors than CK19- cells. Regorafenib preferentially increased the growth inhibition and apoptosis of CK19+ cells in vitro, whereas sorafenib, apatinib, and 5-fluorouracil did not. In PDX models from CK19-/+ HCC patients, the tumor control rate of regorafenib achieved 80% for CK19+ HCCs, whereas 0% for CK19- HCCs. RNA-sequencing revealed that CK19+ cells had elevated expression of mitochondrial ribosomal proteins, which are essential for mitochondrial function. Further experiments confirmed that regorafenib attenuated the mitochondrial respiratory capacity in CK19+ cells. However, the mitochondrial respiration in CK19- cells were faint and hardly repressed by regorafenib. The mitochondrial respiration was regulated by the phosphorylation of signal transducer and activator of transcription 3 (STAT3), which was inhibited by regorafenib in CK19+ cells. Hence, CK19 could be a potential marker of the therapeutic benefit of regorafenib, which facilitates the individualized therapy for HCC. STAT3/mitochondria axis determines the distinct response of CK19+ cells to regorafenib treatment.
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