Huang Hui, Sun Xueying, Zhang Qiqi, Liu Chunyan, Cao Xu, Zhang Duo, Wang Gongchen, Pu Chunwen
Department of Biobank, Dalian Public Health Clinical Center, Dalian, Liaoning 116001, P.R. China.
Dalian Clinical Medical Research Center for Viral Hepatitis, Dalian, Liaoning 116001, P.R. China.
Biomed Rep. 2025 Jul 1;23(3):149. doi: 10.3892/br.2025.2027. eCollection 2025 Sep.
Hepatocellular carcinoma (HCC) is predominantly diagnosed at advanced stages due to a lack of reliable biomarkers for early detection. Consequently, identifying predictive biomarkers for HCC development in patients with chronic liver diseases holds significant potential for improving early diagnosis and clinical outcomes of this aggressive malignancy. Serum levels of immune checkpoint proteins and cytokines were quantified by ELISA in patients with chronic hepatitis B, liver cirrhosis, and HCC, with healthy subjects serving as controls. Cytokine profiles were compared between patients with HCC and without HCC using one-way ANOVA and multivariate logistic regression. The diagnostic performance of interferon (IFN)-γ, interleukin (IL)-22, and α-fetoprotein (AFP) was evaluated by receiver operating characteristic (ROC) curve analysis. The serum levels of programmed cell death protein 1 and programmed death-ligand 1 progressively increased with advancing stages of liver disease. IFN-γ emerged as a protective factor against HCC [odds ratio (OR)=0.991; 95% CI, 0.984-0.997], while IL-22 was identified as a risk factor (OR=1.020, 95% CI, 1.004-1.036). The combined evaluation of IFN-γ and IL-22 demonstrated superior diagnostic accuracy [area under the curve (AUC)=0.863; 95% CI, 0.755-0.971] compared with AFP alone (AUC=0.644; 95% CI, 0.483-0.804). The combination of IFN-γ and IL-22 exhibited enhanced diagnostic performance compared with AFP alone in predicting and detecting early-stage HCC, suggesting its potential utility as a novel biomarker panel for HCC screening.
由于缺乏用于早期检测的可靠生物标志物，肝细胞癌（HCC）主要在晚期被诊断出来。因此，识别慢性肝病患者中HCC发展的预测性生物标志物对于改善这种侵袭性恶性肿瘤的早期诊断和临床结果具有巨大潜力。通过酶联免疫吸附测定（ELISA）对慢性乙型肝炎、肝硬化和HCC患者的血清免疫检查点蛋白和细胞因子水平进行定量，以健康受试者作为对照。使用单因素方差分析和多因素逻辑回归比较HCC患者和非HCC患者的细胞因子谱。通过受试者操作特征（ROC）曲线分析评估干扰素（IFN）-γ、白细胞介素（IL）-22和甲胎蛋白（AFP）的诊断性能。程序性细胞死亡蛋白1和程序性死亡配体1的血清水平随着肝病进展而逐渐升高。IFN-γ成为预防HCC的保护因素[比值比（OR）=0.991；95%置信区间（CI），0.984-0.997]，而IL-22被确定为危险因素（OR=1.020，95%CI，1.004-1.036）。与单独的AFP（曲线下面积（AUC）=0.644；95%CI，0.483-0.804）相比，IFN-γ和IL-22的联合评估显示出更高的诊断准确性（AUC=0.863；95%CI，0.755-0.971）。在预测和检测早期HCC方面，IFN-γ和IL-22的组合与单独的AFP相比表现出更强的诊断性能，表明其作为HCC筛查新型生物标志物组合的潜在效用。
