DNA methylation of SOCS1/2/3 predicts hepatocellular carcinoma recurrence after liver transplantation
DNA methylation of SOCS1/2/3 predicts hepatocellular carcinoma recurrence after liver transplantation
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SOCS1/2/3 DNA甲基化预测肝移植后肝细胞癌复发
DOI：
10.1007/s11033-020-05271-3
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发表时间：
2020-02-01
影响因子：
2.8
通讯作者：
Zheng, Shusen
中科院分区：
文献类型：
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作者：
Yang, Zhentao;Zhu, Hai;Zheng, Shusen
SOCS1/SOCS2/SOCS3基因甲基化状态与肝细胞癌的发生发展密切相关。本研究探讨其对肝移植后肝细胞癌复发的预后价值。对在本中心接受肝移植治疗的62例肝细胞癌患者的临床资料进行了回顾性分析。用下一代测序法测定SOCS1/2/3甲基化水平。总体而言，SOCS1/2/3启动子上的244个甲基化位点被鉴定。多变量分析显示，甲基化位点SOCS2-1-90(12号染色体93963982位；HR 0.386，95%CI 0.149-0.998)和SOCS1-1-68(16号染色体11350699位；HR 4.376，95%CI 1.324-14.459)是肝移植术后复发的独立预测因素。根据SOCS1-1-68(0.95%)和SOCS2-1-90(1.05%)甲基化水平的中位数，患者被分为高度甲基化和低甲基化两组。SOCS2-1-90高度甲基化与甲胎蛋白水平显著降低相关(P= 0.008)，肿瘤最大大小和 8 cm的比例减少(P= 0.02)，病理分级更好(P= 0.06)。相反，高度甲基化的SOCS1-1-68组患者甲胎蛋白水平较高(P= 0.043)。Kaplan-Meier分析显示，SOCS2-1-90高甲基化患者的无复发生存率(RF)和总生存率(OS)均高于低甲基化患者( 分别为0.0041和0.012)。然而，SOCS1-1-68甲基化与累积复发率的相关性不那么明显(P= 0.098)。亚组分析表明，符合米兰标准、UCSF标准、Metroticket 2.0 Model或杭州标准且SOCS2-1-90高度甲基化的患者具有最好的RFS率。SOCS2-1-90基因甲基化是预测肝细胞癌移植后复发的一种新的生物标志物。
DNA methylation status of SOCS1/SOCS2/SOCS3 is intensely involved in the development and progression of hepatocellular carcinoma (HCC). This study explored its prognostic value for HCC recurrence after liver transplantation (LT). Clinical data from 62 HCC patients who underwent LT at our centre were retrospectively collected. The SOCS1/2/3 methylation level were determined using next generation sequencing. Overall, 244 methylated sites at the SOCS1/2/3 promoter were identified. Multivariate analysis yielded the methylated sites SOCS2-1-90 (Chromosome 12, Position 93963982; HR 0.386, 95% CI 0.149–0.998) and SOCS1-1-68 (Chromosome 16, Position 11350699; HR 4.376, 95% CI 1.324–14.459) as independent predictors of post-LT HCC recurrence. Patients were divided into highly- and lowly methylated groups according to the median SOCS1-1-68 (0.95%) and SOCS2-1-90 (1.05%) methylation levels. Highly methylated SOCS2-1-90 was associated with significantly lower AFP levels (P= 0.008), decreased proportion of maximal tumour size > 8 cm (P= 0.02), and better pathological grading (P= 0.06). Conversely, patients in the highly methylated SOCS1-1-68 group had higher AFP levels (P= 0.043). Kaplan–Meier analyses revealed that patients with highly methylated SOCS2-1-90 had increased recurrence free survival (RFS) and overall survival (OS) rates when compared with those with lowly methylated SOCS2-1-90 (P= 0.0041 and 0.012, respectively). Nevertheless, the correlation between methylated SOCS1-1-68 and cumulative recurrence rates was less pronounced (P= 0.098). Subgroup analyses demonstrated that patients meeting the Milan criteria, UCSF criteria, Metroticket 2.0 Model or Hangzhou criteria with highly methylated SOCS2-1-90 had the best RFS rates. DNA methylation of SOCS2-1-90 is a novel biomarker for predicting post-transplant HCC recurrence.