Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China.
Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China; Institute of Hepatology, Shandong University, Jinan, China.
Life Sci. 2021 Apr 1;270:119061. doi: 10.1016/j.lfs.2021.119061. Epub 2021 Jan 14.
For patients with hepatocellular carcinoma (HCC), early detection is critical to improve survival. Secreted frizzled-related protein 2 (SFRP2) is a candidate tumor suppressor as Wnt antagonist and SFRP2 promoter has been found hypermethylated in various malignancies. This study aimed to investigate the methylation status of SFRP2 promoter in hepatitis B virus (HBV) associated HCC and estimate its diagnostic value as a non-invasive biomarker. A total of 293 patients, including 132 patients with HBV-associated HCC, 121 with chronic hepatitis B (CHB) and 40 healthy controls (HCs) were enrolled. SFRP2 methylation level in peripheral mononuclear cells (PBMCs) was quantitatively detected by MethyLight. SFRP2 methylation level was significantly higher in patients with HBV-associated HCC than in those with CHB (p < 0.001) and HCs (p < 0.001) while mRNA level of SFRP2 was significantly lower in HCC group than the other two groups (p < 0.05). In HCC subgroup, SFRP2 methylation level markedly increased in patients >50 years old, female, with negative HBeAg, negative HBV-DNA and poor differentiation compared with the remaining groups (P < 0.05). Furthermore, SFRP2 methylation level showed a significantly better diagnostic value than alpha-fetoprotein (AFP) and the combination of AFP and methylation levels of SFRP2 markedly improved the area under the receiver operating characteristic curve (p < 0.05). In conclusion, hypermethylation of SFRP2 promoter exists in HBV-associated HCC. The combination of SFRP2 methylation level in PBMCs and AFP could significantly improve the diagnostic ability of AFP in discriminating HBV-associated HCC from CHB and SFRP2 methylation level had the potential to serve as a non-invasive biomarker for HCC diagnosis.
对于肝细胞癌（HCC）患者，早期检测对于提高生存率至关重要。分泌卷曲相关蛋白 2（SFRP2）是一种候选肿瘤抑制因子，作为 Wnt 拮抗剂，并且已经在各种恶性肿瘤中发现 SFRP2 启动子超甲基化。本研究旨在研究乙型肝炎病毒（HBV）相关 HCC 中 SFRP2 启动子的甲基化状态，并评估其作为非侵入性生物标志物的诊断价值。共纳入 293 例患者，包括 132 例 HBV 相关 HCC 患者、121 例慢性乙型肝炎（CHB）患者和 40 例健康对照（HC）。通过 MethyLight 定量检测外周血单核细胞（PBMCs）中的 SFRP2 甲基化水平。HBV 相关 HCC 患者的 SFRP2 甲基化水平明显高于 CHB 患者（p<0.001）和 HCs（p<0.001），而 HCC 组的 SFRP2 mRNA 水平明显低于其他两组（p<0.05）。在 HCC 亚组中，与其余组相比，年龄>50 岁、女性、HBeAg 阴性、HBV-DNA 阴性和低分化的患者 SFRP2 甲基化水平明显升高（P<0.05）。此外，SFRP2 甲基化水平的诊断价值明显优于甲胎蛋白（AFP），AFP 与 SFRP2 甲基化水平的联合检测显著提高了接受者操作特征曲线下的面积（p<0.05）。总之，HBV 相关 HCC 中存在 SFRP2 启动子的高甲基化。PBMCs 中 SFRP2 甲基化水平与 AFP 的联合检测可显著提高 AFP 区分 HBV 相关 HCC 与 CHB 的诊断能力，SFRP2 甲基化水平具有作为 HCC 诊断的非侵入性生物标志物的潜力。
