Hypoxia-related and immune phenotype-related fusion model for non-invasive prognostication of hepatocellular carcinoma treated by TACE: a multicentre study.
Authors
Affiliations (16)
Affiliations (16)
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
- Hubei Provincial Clinical Research Center for Precision Radiology & Interventional Medicine, Wuhan, China.
- Hubei Key Laboratory of Molecular Imaging, Wuhan, China.
- Department of Radiology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
- Department of Interventional Radiology, The First College of Clinical Medical Science, Yichang Central People's Hospital, Three Gorges University, Yichang, Hubei, China.
- Department of Interventional Radiology, Guangxi Medical University Cancer Hospital, Guangxi Medical University, Nanning, Guangxi, China.
- Department of Minimally Invasive Intervention, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Peking University Cancer Hospital Yunnan, Kunming, Yunnan, China.
- Department of Interventional Radiology, Guangxi Zhuang Autonomous Region People's Hospital, Nanning, Guangxi, China.
- Department of Interventional Therapy, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China.
- Department of Radiology, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.
- Department of Radiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
- Department of Interventional Radiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
- Department of Oncology, Huanggang Central Hospital of Yangtze University, Huanggang, Hubei, China.
- Hubei Clinical Medical Research Center of Esophageal and Gastric Malignancy, Huanggang, Hubei, China.
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China [email protected] [email protected] [email protected].
Abstract
Survival outcomes after transarterial chemoembolisation (TACE) vary in hepatocellular carcinoma (HCC) patients, and existing prognostic scores and imaging models often lack generalisability and biological interpretability. To develop and validate a multimodal prognostication model for HCC that allows for a precise assessment of survival outcomes of HCC patients receiving TACE therapy. This study enrolled 1448 HCC patients, including a TACE cohort (n=1349), a biomarker subset from a randomised trial (n=41), a single-cell RNA sequencing cohort and The Cancer Genome Atlas (TCGA) HCC cohort (n=50). Pre-treatment contrast-enhanced CT images were used to construct deep learning and conventional radiomic models. The early-fusion and late-fusion models (LFMs) were compared, and a clinical-radiologic model (CRM) was formed by integrating the better-performing LFM with clinical variables. Using TCGA data and single-cell transcriptomic profiles, the differences between high-score and low-score groups in tumour immune microenvironment, cellular functional states and key signalling pathways were investigated. The CRM effectively stratified patients' survival across multiple independent cohorts and achieved more granular risk stratification than the existing clinical models. Multi-omic analyses revealed that in the LFM high-score group, myelocytomatosis oncogene was activated, epithelial-mesenchymal transition enhanced, glycolysis upregulated and hypoxia pathway activated. Single-cell transcriptomic data confirmed that virtually all cell types in high-risk patients scored high in hypoxia, and cytotoxic T cells had a reduced cytotoxic activity. The CRM model can non-invasively predict the prognosis of HCC patients treated by TACE therapy.