European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology · 2025
Development of a circulating tumor DNA methylation biomarker panel for hepatocellular carcinoma detection.
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Zhou Yanzhao, Zhang Beilin, Yang Ke, Wang Zhengzheng, Li Qingjun, Wang Weizhen, Chen Dongxu, Ma Jie, Zhou Jinxue
Аннотация
INTRODUCTION: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. Early detection is crucial for improving the overall survival rates in patients diagnosed with HCC.
MATERIALS AND METHODS: In this study, we developed a novel methylation-based gene panel for HCC detection using a large cohort of 149 patients with HCC and 270 controls, which included 109 healthy individuals, 102 patients with benign liver diseases, and 59 patients with non-hepatic malignancies. The diagnostic performance of the panel was assessed by generating receiver operating characteristic (ROC) curves to determine the area under the curve (AUC), sensitivity, specificity, and corresponding 95 % confidence intervals (CIs). All statistical figures were generated using GraphPad Prism software.
RESULTS: Our analysis revealed significantly elevated methylation levels of SEPTIN9, Suppressor of Cytokine Signaling 1 (SOCS1), and Cyclooxygenase-2 (COX2) in HCC patients compared to those in all control groups. The panel demonstrated strong diagnostic performance, achieving an AUC of 0.907 (95 % CI: 0.876-0.933), with a sensitivity of 83.9 % (95 % CI: 77.0-89.4 %) and a specificity of 88.5 % (95 % CI: 84.1-92.1 %). Importantly, it exhibited high diagnostic efficacy for early stage HCC, achieving sensitivities of 75.0 % for stage I and 84.0 % for stage II. Comparisons with pathological findings yielded a kappa value of 0.72, indicating a substantial agreement with the gold standard.
CONCLUSION: These findings suggest that the DNA methylation biomarkers panel could revolutionize HCC diagnostics by enabling earlier, more accurate, and cost-effective detection, particularly in high-risk populations.
MATERIALS AND METHODS: In this study, we developed a novel methylation-based gene panel for HCC detection using a large cohort of 149 patients with HCC and 270 controls, which included 109 healthy individuals, 102 patients with benign liver diseases, and 59 patients with non-hepatic malignancies. The diagnostic performance of the panel was assessed by generating receiver operating characteristic (ROC) curves to determine the area under the curve (AUC), sensitivity, specificity, and corresponding 95 % confidence intervals (CIs). All statistical figures were generated using GraphPad Prism software.
RESULTS: Our analysis revealed significantly elevated methylation levels of SEPTIN9, Suppressor of Cytokine Signaling 1 (SOCS1), and Cyclooxygenase-2 (COX2) in HCC patients compared to those in all control groups. The panel demonstrated strong diagnostic performance, achieving an AUC of 0.907 (95 % CI: 0.876-0.933), with a sensitivity of 83.9 % (95 % CI: 77.0-89.4 %) and a specificity of 88.5 % (95 % CI: 84.1-92.1 %). Importantly, it exhibited high diagnostic efficacy for early stage HCC, achieving sensitivities of 75.0 % for stage I and 84.0 % for stage II. Comparisons with pathological findings yielded a kappa value of 0.72, indicating a substantial agreement with the gold standard.
CONCLUSION: These findings suggest that the DNA methylation biomarkers panel could revolutionize HCC diagnostics by enabling earlier, more accurate, and cost-effective detection, particularly in high-risk populations.