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Updated: May 9, 2026
Non-Invasive PET/MR Imaging in an Orthotopic Mouse Model of Hepatocellular Carcinoma
Published on: August 31, 2022
Radiogenomics deciphers tumor heterogeneity in hepatocellular carcinoma and combined
Yi Wang1, Shichen Miao2, Xiao Wang3
1Department of Hepatobiliary Surgery and Liver Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Background:
Combined hepatocellular cholangiocarcinoma (cHCC-CCA) is a highly heterogeneous cancer with limited knowledge of molecular features and prognosis. To compare the molecular features of cHCC-CCA with different subtypes of hepatocellular carcinoma (HCC) and to investigate the biological meanings of prognostic radiomic features in cHCC-CCA.
Methods:
We performed an integrative analysis to investigate the heterogeneity of cHCC-CCA and HCC by combining transcriptomic and radiomic approaches. RNA sequencing revealed distinct transcriptomic profiles between cHCC-CCA and HCC. For radiomic analysis, an eight-feature radiomic signature was constructed using preoperative contrast-enhanced MRI to predict overall survival in cHCC-CCA, and its prognostic significance was validated in an external dataset. Furthermore, weighted gene co-expression network analysis was employed to correlate radiomic features with underlying biological pathways.
Results:
LR-M subtype of cHCC-CCA exhibited more aggressive characteristics and immunosuppressive tumor microenvironment compared with LR-4/5 subtype, HCC with rim arterial-phase hyperenhancement (rim-APHE) and HCC without rim-APHE. The radiomic signature was correlated with overall survival (hazard ratio [HR], 5.47; 95% CI:2.08, 7.23, p = 0.006) in the cHCC-CCA validation cohort. Three types of prognostic radiomic features were correlated with distinct pathways: fatty acid metabolism, signaling pathways regulating pluripotency of stem cells and T cell receptor signaling pathway, respectively. Original_Glszm_GrayLevelNonUniformity might reflect the upregulation of fatty acid metabolism and immune suppression of cHCC-CCA.
Conclusions:
We illustrated the heterogeneity of subtypes of HCC and cHCC-CCA, which provides insights into the differentiation of primary liver cancer. Correlation of prognostic radiomic features with transcriptome profiles in cHCC-CCA enables noninvasive evaluation of tumor microenvironment.
