Epigenomics AG, Geneststr. 5, 10829, Berlin, Germany.
Epigenomics Inc., 11055 Flintkote Ave, Suite A, San Diego, CA, 92121, USA.
BMC Gastroenterol. 2021 Mar 25;21(1):136. doi: 10.1186/s12876-021-01714-8.
Hepatocellular carcinoma (HCC) is the leading cause of death in patients with cirrhosis, primarily due to failed early detection. HCC screening is recommended among individuals with cirrhosis using biannual abdominal ultrasound, for earlier tumor detection, administration of curative treatment, and improved survival. Surveillance by imaging with or without biomarkers such as alpha-fetoprotein (AFP) remains suboptimal for early stage HCC detection. Here we report on the development and assessment of methylation biomarkers from liquid biopsies for HCC surveillance in cirrhotic patients.
DNA methylation markers including the HCCBloodTest (Epigenomics AG) and a DNA-methylation panel established by next generation sequencing (NGS) were assessed using a training/testing design. The NGS panel algorithm was established in a training study (41 HCC patients; 46 cirrhotic non-HCC controls). For testing, plasma samples were obtained from cirrhotic patients (Child class A or B) with (60) or without (103) early stage HCC (BCLC stage 0, A, B). The assays were then tested using blinded sample sets and analyzed by preset algorithms.
The HCCBloodTest and the NGS panel exhibited 76.7% and 57% sensitivities at 64.1% and 97% specificity, respectively. In a post-hoc analysis, a combination of the NGS panel with AFP (20 ng/mL) achieved 68% sensitivity at 97% specificity (AUC = 0.9).
Methylation biomarkers in cell free plasma DNA provide a new alternative for HCC surveillance. Multiomic panels comprising DNA methylation markers with other biological markers, such as AFP, provide an option to further increase the overall clinical performance of surveillance via minimally invasive blood samples.
Test set study-ClinicalTrials.gov (NCT03804593) January 11, 2019, retrospectively registered.
肝细胞癌 (HCC) 是肝硬化患者死亡的主要原因，主要是因为早期检测失败。建议对肝硬化患者进行 HCC 筛查，每半年进行一次腹部超声检查，以便更早地发现肿瘤，进行有治愈可能的治疗，并提高生存率。使用生物标志物（如甲胎蛋白 [AFP]）联合或不联合影像学的监测对于早期 HCC 的检测仍然不够理想。在这里，我们报告了用于肝硬化患者 HCC 监测的液体活检中甲基化生物标志物的开发和评估。
使用训练/测试设计评估了包括 HCCBloodTest（Epigenomics AG）和通过下一代测序（NGS）建立的 DNA 甲基化面板在内的 DNA 甲基化标记物。NGS 面板算法是在一项训练研究中（41 名 HCC 患者；46 名肝硬化非 HCC 对照）建立的。在测试中，从肝硬化患者（Child 分级 A 或 B）中获得血浆样本，这些患者患有（60 名）或未患有（103 名）早期 HCC（BCLC 分期 0、A、B）。然后使用盲样集测试这些检测，并根据预设算法进行分析。
HCCBloodTest 和 NGS 面板的灵敏度分别为 76.7%和 57%，特异性分别为 64.1%和 97%。在事后分析中，NGS 面板与 AFP（20ng/mL）的组合在 97%的特异性下实现了 68%的灵敏度（AUC=0.9）。
无细胞游离血浆 DNA 中的甲基化生物标志物为 HCC 监测提供了一种新的选择。由 DNA 甲基化标记物与其他生物标志物（如 AFP）组成的多组学面板为通过微创血液样本进一步提高监测的整体临床性能提供了一种选择。
测试集研究-ClinicalTrials.gov（NCT03804593），2019 年 1 月 11 日，回顾性注册。
