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长散在核元件 1 低甲基化通过激活人肝癌中的 ST18 与不良预后相关。

Long interspersed nuclear element-1 hypomethylation is associated with poor outcomes via the activation of ST18 in human hepatocellular carcinoma.

机构信息

Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital.

Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University.

出版信息

Medicine (Baltimore). 2021 Apr 23;100(16):e25552. doi: 10.1097/MD.0000000000025552.

Abstract

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.

摘要

长散在核元件-1(LINE-1)甲基化水平代表脱氧核糖核酸的整体甲基化水平,可能通过激活癌基因影响癌症的预后。本研究旨在评估肝癌(HCC)患者 LINE-1 低甲基化的预后意义,以及与癌基因激活相关的可能机制。

本前瞻性研究纳入了 2014 年 10 月至 2015 年 9 月期间的 77 例 HCC 患者。采用定量焦磷酸测序法评估 HCC 和配对非 HCC 组织样本的 LINE-1 甲基化水平。采用免疫组织化学法检测抑瘤素 18 的表达,并检测其与 LINE-1 甲基化水平的相关性。

与配对的非肿瘤组织相比,HCC 组织中的 LINE-1 明显低甲基化(64.0±11.6%比 75.6±4.0%,P<0.001)。LINE-1 低甲基化是总生存期(风险比=27.291,P=0.032)和疾病进展(风险比=5.298,P=0.005)的独立危险因素。低甲基化 LINE-1 HCC 组织中抑瘤素 18 的表达高于高甲基化 LINE-1 肿瘤组织(P=0.030)。

LINE-1 低甲基化可能是 HCC 患者潜在的预后标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2897/8078304/3654667cf549/medi-100-e25552-g001.jpg

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