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Deciphering intratumoral heterogeneity of hepatocellular carcinoma with microvascular invasion with radiogenomic analysis

Authors :
Yi Wang
Gui-Qi Zhu
Rui Yang
Cheng Wang
Wei-Feng Qu
Tian-Hao Chu
Zheng Tang
Chun Yang
Li Yang
Chang-Wu Zhou
Geng-Yun Miao
Wei-Ren Liu
Ying-Hong Shi
Meng-Su Zeng
Source :
Journal of Translational Medicine, Vol 21, Iss 1, Pp 1-15 (2023)
Publication Year :
2023
Publisher :
BMC, 2023.

Abstract

Abstract Background and aims The recurrence and metastasis of hepatocellular carcinoma (HCC) are mainly caused by microvascular invasion (MVI). Our study aimed to uncover the cellular atlas of MVI+ HCC and investigate the underlying immune infiltration patterns with radiomics features. Methods Three MVI positive HCC and three MVI negative HCC samples were collected for single-cell RNA-seq analysis. 26 MVI positive HCC and 30 MVI negative HCC tissues were underwent bulk RNA-seq analysis. For radiomics analysis, radiomics features score (Radscore) were built using preoperative contrast MRI for MVI prediction and overall survival prediction. We deciphered the metabolism profiles of MVI+ HCC using scMetabolism and scFEA. The correlation of Radscore with the level of APOE+ macrophages and iCAFs was identified. Whole Exome Sequencing (WES) was applied to distinguish intrahepatic metastasis (IM) and multicentric occurrence (MO). Transcriptome profiles were compared between IM and MO. Results Elevated levels of APOE+ macrophages and iCAFs were detected in MVI+ HCC. There was a strong correlation between the infiltration of APOE+ macrophages and iCAFs, as confirmed by immunofluorescent staining. MVI positive tumors exhibited increased lipid metabolism, which was attributed to the increased presence of APOE+ macrophages. APOE+ macrophages and iCAFs were also found in high levels in IM, as opposed to MO. The difference of infiltration level and Radscore between two nodules in IM was relatively small. Furthermore, we developed Radscore for predicting MVI and HCC prognostication that were also able to predict the level of infiltration of APOE+ macrophages and iCAFs. Conclusion This study demonstrated the interactions of cell subpopulations and distinct metabolism profiles in MVI+ HCC. Besides, MVI prediction Radscore and MVI prognostic Radscore were highly correlated with the infiltration of APOE+ macrophages and iCAFs, which helped to understand the biological significance of radiomics and optimize treatment strategy for MVI+ HCC.

Details

Language :
English
ISSN :
14795876
Volume :
21
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Journal of Translational Medicine
Publication Type :
Academic Journal
Accession number :
edsdoj.5651ab69d4fe40a8b1204f84ae77620f
Document Type :
article
Full Text :
https://doi.org/10.1186/s12967-023-04586-6