Department of Internal Medicine, Yale School of Medicine, New Haven, CT, United States.
University of Hawai'i Cancer Consortium, Honolulu, HI, United States.
Biosci Rep. 2024 Mar 29;44(3). doi: 10.1042/BSR20232063.
Alterations to DNA methylation have been identified in both hepatocellular carcinoma (HCC) tumor and circulating DNA from affected individuals. These markers have potential utility in HCC screening. Adherence to HCC screening is poor and acceptable HCC screening tests are needed.
A feasibility study was performed on a subset of case patients and control subjects from a prior study of risk factors for HCC. Case patients (n=12) included adults aged 47-85 years with a first diagnosis of HCC between 2011 and 2016 and without viral hepatitis. Control subjects (n=12) were matched on age, sex, and state of residence. Participants provided saliva samples for DNA genotyping. Log fold change in salivary DNA methylation at 1359 CpG sites representing 25 candidate genes previously associated with HCC was compared across case patients and control subjects.
The quantity of DNA ranged from 9.65 to 257.79 μg. The purity of DNA isolates was good, with mean OD260/280 ratio of 1.78 (SD: 0.14). Of 25 candidate genes, 16 had at ≥1 CpG site with detectable differences in methylation across HCC case patients and control subjects. Sites differentially methylated in HCC case patients included genes encoding tumor suppressors (PRDM2, RUNX3, p15/16, and RASSF1/5), regulators of cell cycle progression (DAPK1 and TP73), and DNA repair (MGMT and GSTP1). No associations met the significance threshold 3.7 × 10-5 required for multiple comparisons.
Salivary DNA may be a feasible alternative to blood samples in the era of novel DNA-based screening tests for HCC. The ease of saliva-based testing supports further investigation of its potential.
在肝癌（HCC）肿瘤和受影响个体的循环 DNA 中均发现了 DNA 甲基化的改变。这些标志物在 HCC 筛查中有潜在的应用价值。但是 HCC 筛查的依从性很差，因此需要有可接受的 HCC 筛查测试。
对先前 HCC 危险因素研究中的病例患者和对照患者的亚组进行了一项可行性研究。病例患者（n=12）包括年龄在 47-85 岁之间的成年人，他们在 2011 年至 2016 年间首次诊断出 HCC，并且没有病毒性肝炎。对照患者（n=12）在年龄、性别和居住地方面与病例患者相匹配。参与者提供了用于 DNA 基因分型的唾液样本。比较了病例患者和对照患者之间代表先前与 HCC 相关的 25 个候选基因的 1359 个 CpG 位点的唾液 DNA 甲基化的对数倍变化。
DNA 的量范围为 9.65 至 257.79μg。DNA 分离物的纯度良好，平均 OD260/280 比值为 1.78（SD：0.14）。在 25 个候选基因中，有 16 个基因的至少 1 个 CpG 位点的甲基化在 HCC 病例患者和对照患者之间存在可检测到的差异。在 HCC 病例患者中甲基化差异的位点包括编码肿瘤抑制因子（PRDM2、RUNX3、p15/16 和 RASSF1/5）、细胞周期进展调节剂（DAPK1 和 TP73）和 DNA 修复（MGMT 和 GSTP1）的基因。没有一个位点达到了多重比较所需的 3.7×10-5 的显著性阈值。
在基于新型 DNA 的 HCC 筛查试验的时代，唾液 DNA 可能是血液样本的可行替代方法。基于唾液的检测方法的简便性支持进一步研究其潜力。
