Long interspersed nuclear element-1 hypomethylation is associated with poor outcomes via the activation of ST18 in human hepatocellular carcinoma.
Long interspersed nuclear element-1 hypomethylation is associated with poor outcomes via the activation of ST18 in human hepatocellular carcinoma.
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DOI：
10.1097/md.0000000000025552
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发表时间：
2021-04-23
期刊：
影响因子：
1.6
通讯作者：
Hur K
中科院分区：
文献类型：
--
作者：
Lee YR;Kim G;Lee HW;Tak WY;Park SY;Jang SY;Kweon YO;Park JG;Han YS;Chun JM;Han JR;Hur K
长散布核元件 1 (LINE-1) 甲基化水平代表整体脱氧核糖核酸甲基化水平，可能通过癌基因的激活有助于癌症的预后。本研究旨在评估 LINE-1 低甲基化对肝细胞癌 (HCC) 患者的预后影响以及与癌基因激活相关的可能机制。 2014 年 10 月至 2015 年 9 月期间的 77 名 HCC 患者参加了这项前瞻性研究。进行定量焦磷酸测序以评估 HCC 和匹配的非 HCC 组织样本的 LINE-1 甲基化水平。通过免疫组织化学测定致瘤性抑制18的表达，并检查其与LINE-1甲基化水平的相关性。与匹配的非肿瘤组织相比，HCC 组织中的 LINE-1 显着低甲基化（64.0 ± 11.6% vs 75.6±4.0%，P< .001）。 LINE-1 低甲基化是总生存（风险比 = 27.291，P = .032）和疾病进展（风险比 = 5.298，P = .005）的独立危险因素。低甲基化的LINE-1 HCC组织中致瘤性抑制18的表达高于高甲基化的LINE-1肿瘤组织（P = .030）。 LINE-1 低甲基化可能作为 HCC 患者的潜在预后标志物。
The level of long interspersed nuclear element-1 (LINE-1) methylation, representing the global deoxyribonucleic acid methylation level, could contribute to the prognosis of cancer via the activation of oncogenes. This study was performed to evaluate the prognostic implications of LINE-1 hypomethylation in patients with hepatocellular carcinoma (HCC) and the possible mechanisms related to oncogene activation. Seventy-seven HCC patients between October 2014 and September 2015 were enrolled in this prospective study. Quantitative pyrosequencing was performed to assess the LINE-1 methylation level of HCC and matched non-HCC tissue samples. The expression of suppression of tumorigenicity 18 was measured by immunohistochemistry and its correlation with LINE-1 methylation levels was examined. LINE-1 was significantly hypomethylated in the HCC tissue compared with the matched nontumor tissue (64.0 ± 11.6% vs 75.6 ± 4.0%, P < .001). LINE-1 hypomethylation was an independent risk factor for overall survival (hazard ratio = 27.291, P = .032) and disease progression (hazard ratio = 5.298, P = .005). The expression of suppression of tumorigenicity 18 was higher in the hypomethylated LINE-1 HCC tissue than the hypermethylated LINE-1 tumor tissue (P = .030). LINE-1 hypomethylation may serve as a potential prognostic marker for patients with HCC.