Artusa Fabian, Lamatsch Sven, Phan Minh Duc, Özdirik Burcin, Berger Hilmar, Egerer Mara, Knorr-Klocke Jana, Fischer Janett, Veelken Rhea, van Bömmel Florian, Berg Thomas, Kappert Kai, Tauber Rudolf, Puengel Tobias, Engelmann Cornelius, Demir Münevver, Tacke Frank, Mohr Raphael
Department of Hepatology and Gastroenterology, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM), Berlin, Germany.
Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany.
Liver Int. 2025 Jun;45(6):e70121. doi: 10.1111/liv.70121.
The introduction of immune checkpoint inhibitor (ICI) based therapies has significantly improved the prognosis of patients with unresectable hepatocellular carcinoma (HCC). However, the variable treatment response and the uncertain benefit in patients with advanced liver cirrhosis emphasise the urgent need for prognostic and predictive biomarkers guiding patient selection. The soluble urokinase plasminogen activator receptor (suPAR) is strongly associated with inflammation, liver cirrhosis and various types of cancer. In this study, we investigated suPAR as a potential novel biomarker in patients with unresectable HCC.
This multicenter retrospective study, conducted at three German tertiary care centers, included 90 patients with unresectable HCC and suPAR measurements prior to and during atezolizumab/bevacizumab therapy. Patients with liver cirrhosis without HCC (n = 235) and non-cirrhotic patients with other gastrointestinal tumours (n = 155) were selected as control cohorts.
Median suPAR levels were significantly higher in patients with liver cirrhosis compared to non-cirrhotic cancer patients. A strong association with parameters of liver function, but not with HCC characteristics, was observed. In patients with HCC receiving atezolizumab/bevacizumab, suPAR was the most accurate independent predictor of hepatic decompensation and overall survival (OS). In addition, suPAR was able to stratify the risk of hepatic decompensation within the different Child-Pugh classes.
SuPAR represents a promising novel biomarker in patients with HCC treated with ICI-based therapies and bears the potential to guide the selection of antitumoral systemic therapies in patients with advanced liver cirrhosis.
基于免疫检查点抑制剂（ICI）的疗法的引入显著改善了不可切除肝细胞癌（HCC）患者的预后。然而，晚期肝硬化患者的治疗反应多变且获益不确定，这凸显了迫切需要用于指导患者选择的预后和预测生物标志物。可溶性尿激酶型纤溶酶原激活物受体（suPAR）与炎症、肝硬化及各类癌症密切相关。在本研究中，我们调查了suPAR作为不可切除HCC患者潜在的新型生物标志物的情况。
这项在德国三个三级医疗中心开展的多中心回顾性研究纳入了90例不可切除HCC患者，这些患者在接受阿替利珠单抗/贝伐珠单抗治疗之前及治疗期间均进行了suPAR检测。选取无HCC的肝硬化患者（n = 235）和患有其他胃肠道肿瘤的非肝硬化患者（n = 155）作为对照队列。
与非肝硬化癌症患者相比，肝硬化患者的suPAR中位数水平显著更高。观察到suPAR与肝功能参数密切相关，但与HCC特征无关。在接受阿替利珠单抗/贝伐珠单抗治疗的HCC患者中，suPAR是肝失代偿和总生存期（OS）最准确的独立预测指标。此外，suPAR能够在不同Child-Pugh分级中对肝失代偿风险进行分层。
在接受基于ICI疗法的HCC患者中，suPAR是一种有前景的新型生物标志物，并且有可能指导晚期肝硬化患者抗肿瘤全身治疗的选择。
