Gene/protein analysis to determine the cause of immune anticancer resistance for invasive hepatocellular carcinoma
Nov 27, 2025
Oncology department at Cha Medical University Bundang Cha Hospital (Director Yoon Sang-wook) Cancer Center Jeon Hong-jae, Kim Chan-seok, research professor Lee Won-seok and pathology professor Hwang Woo-hyun analyzed clinical, imaging, and genetic information on patients with advanced hepatocellular carcinoma to reveal the characteristics of invasive liver cancer that can predict the effect of combined immune anticancer drug treatment in advance. The study was published in the latest issue of the international journal Clinical and Molecular Heptology (IF=16.9).
The research team analyzed 307 patients who received the combination treatment of atezolizumab and bevacizumab in patients with advanced hepatocellular carcinoma. Based on imaging images, tumor morphology was classified into four types, and 42.7% of all patients accounted for type IV 'invasive'. Among them, only 14.6% responded to immuno-oncology treatment, the median progression-free survival period was 2.8 months, and the median overall survival period was 7.1 months, showing significantly lower survival rates than other types of liver cancer patients. Even if all various clinical factors such as age, liver function, and treatment history are considered, it has been confirmed that 'invasive' is an independent indicator for predicting the poor prognosis of hepatocellular carcinoma.
The research team identified the characteristics of invasive hepatocellular carcinoma through integrated analysis of genomes, transcripts, and proteins. In genome analysis, mutations with loss of function of TP53 and ATM genes were observed at high frequency, confirming that biological pathways that increase cancer invasiveness and treatment resistance, such as cell proliferation, epithelial and mesenchymal conversion (EMT), TGF-β signal activation, and immunosuppressive tumor microenvironment formation, were activated. In particular, it was found that the infiltration of regulatory T cells (Tregs) increased clearly, creating an immunosuppressive tumor microenvironment, acting as a major cause of the decline in immune anticancer drug response. In addition, analysis through five external independent cohorts, including 'IMbrave150', confirmed that invasive gene signature showed a significant association with low survival rates in hepatocellular carcinoma patients, and this signature can be used as an indicator to predict patient prognosis and plan treatment.
Most of the existing studies on invasive hepatocellular carcinoma have analyzed imaging, clinical, and dielectric information comprehensively at the level of observing the tumor shape with CT and MRI images or estimating the prognosis only with clinical information such as the patient's age and liver function. This study is expected to provide an important basis for establishing a customized treatment strategy for liver cancer patients as it has been identified by integrating molecular information such as invasive tumors, genes, proteins, and immune environments that can be confirmed by video.
Professor Jeon Hong-jae of Oncology said, "This study goes beyond just the morphological classification of hepatocellular carcinoma, and it is a meaningful study that analyzes how invasive tumors show resistance to immune anticancer drugs and have low survival rates at the molecular level.".
This study was conducted with the support of the Ministry of Science and ICT and the Korea Research Foundation's mid-sized research support project and the Ministry of Health and Welfare and the Korea Health Industry Promotion Agency's global apple scholar training project.
The research team analyzed 307 patients who received the combination treatment of atezolizumab and bevacizumab in patients with advanced hepatocellular carcinoma. Based on imaging images, tumor morphology was classified into four types, and 42.7% of all patients accounted for type IV 'invasive'. Among them, only 14.6% responded to immuno-oncology treatment, the median progression-free survival period was 2.8 months, and the median overall survival period was 7.1 months, showing significantly lower survival rates than other types of liver cancer patients. Even if all various clinical factors such as age, liver function, and treatment history are considered, it has been confirmed that 'invasive' is an independent indicator for predicting the poor prognosis of hepatocellular carcinoma.
The research team identified the characteristics of invasive hepatocellular carcinoma through integrated analysis of genomes, transcripts, and proteins. In genome analysis, mutations with loss of function of TP53 and ATM genes were observed at high frequency, confirming that biological pathways that increase cancer invasiveness and treatment resistance, such as cell proliferation, epithelial and mesenchymal conversion (EMT), TGF-β signal activation, and immunosuppressive tumor microenvironment formation, were activated. In particular, it was found that the infiltration of regulatory T cells (Tregs) increased clearly, creating an immunosuppressive tumor microenvironment, acting as a major cause of the decline in immune anticancer drug response. In addition, analysis through five external independent cohorts, including 'IMbrave150', confirmed that invasive gene signature showed a significant association with low survival rates in hepatocellular carcinoma patients, and this signature can be used as an indicator to predict patient prognosis and plan treatment.
Most of the existing studies on invasive hepatocellular carcinoma have analyzed imaging, clinical, and dielectric information comprehensively at the level of observing the tumor shape with CT and MRI images or estimating the prognosis only with clinical information such as the patient's age and liver function. This study is expected to provide an important basis for establishing a customized treatment strategy for liver cancer patients as it has been identified by integrating molecular information such as invasive tumors, genes, proteins, and immune environments that can be confirmed by video.
Professor Jeon Hong-jae of Oncology said, "This study goes beyond just the morphological classification of hepatocellular carcinoma, and it is a meaningful study that analyzes how invasive tumors show resistance to immune anticancer drugs and have low survival rates at the molecular level.".
This study was conducted with the support of the Ministry of Science and ICT and the Korea Research Foundation's mid-sized research support project and the Ministry of Health and Welfare and the Korea Health Industry Promotion Agency's global apple scholar training project.
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This article was translated by Naver AI translator.
