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Updated: Dec 22, 2025

A Three-Dimensional Spheroid Model to Investigate the Tumor-Stromal Interaction in Hepatocellular Carcinoma
Published on: September 30, 2021
Tumour budding and tumour-stroma ratio in hepatocellular carcinoma
Valtteri Kairaluoma1, Niko Kemi2, Vesa-Matti Pohjanen2
1Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland. valtteri.kairaluoma@oulu.fi.
Background:
Tumour budding and low tumour-stroma ratio (TSR) are associated with poor prognosis in some cancers, but their value in Western hepatocellular carcinoma is unclear. The prognostic value of tumour budding and TSR in hepatocellular carcinoma was examined.
Methods:
Some 259 hepatocellular carcinoma patients treated in Oulu University Hospital 1983-2018 were included in this retrospective cohort study. Tumour budding and TSR were analysed from the haematoxylin- and eosin-stained original diagnostic slides, by dividing patients into bud-negative (0 bud) or bud-positive (≥1 bud) groups, and into high TSR (<50%) and low TSR (≥50%) groups. Surgically treated patients (n = 47) and other treatments (n = 212) were analysed separately. Primary outcomes were overall, and disease-specific 5-year mortality was adjusted for confounding factors.
Results:
Surgically treated patients with positive tumour budding had increased 5-year overall (adjusted HR 3.87, 95% CI 1.10-13.61) and disease-specific (adjusted HR 6.17, 95% CI 1.19-31.90) mortality compared with bud-negative patients. In surgically treated patients, TSR had no effect on 5-year overall (adjusted HR 2.03, 95% CI 0.57-7.21) or disease-specific (adjusted HR 3.23, 95% CI 0.78-13.37) mortality. No difference in survival related to tumour budding and TSR in non-surgically treated patients was observed.
Conclusions:
Tumour budding is a prognostic factor in surgically treated hepatocellular carcinoma.
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