Prognostic value of LINE-1 methylation level in 321 patients with primary liver cancer including hepatocellular carcinoma and intrahepatic cholangiocarcinoma.
Prognostic value of LINE-1 methylation level in 321 patients with primary liver cancer including hepatocellular carcinoma and intrahepatic cholangiocarcinoma.
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DOI：
10.18632/oncotarget.25124
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发表时间：
2018-04-17
期刊：
影响因子：
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通讯作者：
Baba H
中科院分区：
文献类型：
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作者：
Miyata T;Yamashita YI;Baba Y;Harada K;Yamao T;Umezaki N;Tsukamoto M;Kitano Y;Yamamura K;Arima K;Nakagawa S;Okabe H;Imai K;Hashimoto D;Chikamoto A;Shimokawa M;Baba H
长穿插核苷酸元件-1 （long interspersed nucleotide element-1, LINE-1）甲基化水平是整体DNA甲基化水平的良好替代标记。原发性肝癌（PLC）患者LINE-1甲基化水平与预后的关系尚不清楚。LINE-1甲基化水平在HCC和cHCC-CC组织中显著低于非癌性肝实质组织，但在ICC组织中没有（HCC: p < 0.0001; cHCC-CC: p < 0.001; ICC: p = 0.053）。低甲基化LINE-1的HCC患者无复发生存期（RFS）显著缩短（log-rank, p = 0.008）；然而，在cHCC-CC或ICC案件中没有观察到这种情况。多因素Cox回归分析显示，低甲基化LINE-1组的HCC复发率显著较高（风险比1.62；95%可信区间1.06-2.58;p = 0.025）。通过LINE-1甲基化水平估计的全基因组DNA低甲基化状态可能指示HCC患者的RFS较差，但不指示ICC或cHCC-CC。我们通过福尔马林固定石蜡包埋（FFPE）组织的磷酸测序，评估了321例治愈切除的PLC（231例肝细胞癌（HCC）， 19例肝细胞胆管合并癌（cHCC-CC）和71例肝内胆管癌（ICC））的LINE-1甲基化水平，并研究了其预后价值。
The methylation level of long interspersed nucleotide element-1 (LINE-1) is a good surrogate marker of the global DNA methylation level. The relationship between LINE-1 methylation level and prognosis in primary liver cancer (PLC) patients remains unclear. LINE-1 methylation levels were significantly lower in HCC and cHCC-CC tissues, but not in ICC tissues, than those in noncancerous liver parenchyma (HCC: p < 0.0001; cHCC-CC: p < 0.001; and ICC: p = 0.053). HCC cases with hypomethylated LINE-1 had significantly shorter relapse-free survival (RFS) (log-rank, p = 0.008); however, this was not observed for the cHCC-CC or ICC cases. Multivariate Cox regression analysis revealed a significantly higher HCC recurrence rate in the group with hypomethylated LINE-1 (hazard ratio, 1.62; 95% confidence interval, 1.06–2.58; p = 0.025). The genome-wide DNA hypomethylation status estimated via LINE-1 methylation levels might be indicative of poor RFS in patients with HCC but not ICC or cHCC-CC. We evaluated the level of LINE-1 methylation in 321 cases of curatively resected PLC {231 hepatocellular carcinoma (HCC), 19 combined hepatocellular and cholangiocarcinoma (cHCC-CC) and 71 intrahepatic cholangiocarcinoma (ICC)} via pyrosequencing of formalin-fixed paraffin-embedded (FFPE) tissues and examined its prognostic value.