Ye Ding, Jiang Danjie, Li Yingjun, Jin Mingjuan, Chen Kun
Department of Epidemiology and Health Statistics, Zhejiang University School of Public Health, 866 Yuhangtang Road, Hangzhou, 310058, China.
Department of Public Health, Hangzhou Medical School, Hangzhou, China.
Int J Clin Oncol. 2017 Aug;22(4):749-757. doi: 10.1007/s10147-017-1106-1. Epub 2017 Mar 25.
The prognostic value of long interspersed nucleotide element-1 (LINE-1) methylation in patients with colorectal cancer (CRC) remains uncertain. We have therefore performed a meta-analysis to elucidate this issue.
The PubMed and Web of Science databases were searched for studies published up to 30 June 2016 which reported on an association between LINE-1 methylation and overall survival (OS), disease-free survival (DFS), or cancer-specific survival (CSS) among CRC patients. The reference lists of the identified studies were also analyzed to identify additional eligible studies. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using the fixed-effects or the random-effects model. Stratification analysis and meta-regression analysis were performed to detect the source of heterogeneity. Analyses of sensitivity and publication bias were also carried out.
Thirteen independent studies involving 3620 CRC patients were recruited to the meta-analysis. LINE-1 hypomethylation was found to be significantly associated with shorter OS (HR 2.92, 95% CI 2.20-3.88, p < 0.001) and DFS (HR 2.18, 95% CI 1.46-3.27, p < 0.001), as well as unfavorable CSS (HR 1.96, 95% CI 1.35-2.85, p < 0.001). No heterogeneity was found among the studies evaluating the associations between LINE-1 hypomethylation and OS or DFS, with the exception being CSS. Moreover, meta-regression analysis suggested that one of the contributors to between-study heterogeneity on the association between LINE-1 methylation and CSS was statistical methodology. The subgroup analysis suggested that the association in studies using the Cox model statistical method (HR 2.76, 95% CI 1.90-4.01, p < 0.001) was stronger than that in studies using the Log-rank test (HR 1.41, 95% CI 1.07-1.87, p = 0.015).
The results of this meta-analysis suggest that LINE-1 methylation is significantly associated with the survival of CRC patients and that it could be a predictive factor for CRC prognosis.
长散在核苷酸元件1（LINE-1）甲基化在结直肠癌（CRC）患者中的预后价值仍不确定。因此，我们进行了一项荟萃分析以阐明这一问题。
检索PubMed和Web of Science数据库，查找截至2016年6月30日发表的关于CRC患者中LINE-1甲基化与总生存期（OS）、无病生存期（DFS）或癌症特异性生存期（CSS）之间关联的研究。还对已确定研究的参考文献列表进行分析，以确定其他符合条件的研究。采用固定效应模型或随机效应模型汇总95%置信区间（CI）的风险比（HR）。进行分层分析和meta回归分析以检测异质性来源。还进行了敏感性分析和发表偏倚分析。
13项涉及3620例CRC患者的独立研究被纳入荟萃分析。发现LINE-1低甲基化与较短的OS（HR 2.92，95%CI 2.20 - 3.88，p < 0.001）、DFS（HR 2.18，95%CI 1.46 - 3.27，p < 0.001）以及不良CSS（HR 1.96，95%CI 1.35 - 2.85，p < 0.001）显著相关。在评估LINE-1低甲基化与OS或DFS之间关联的研究中未发现异质性，但CSS相关研究除外。此外，meta回归分析表明，LINE-1甲基化与CSS之间研究间异质性的一个原因是统计方法。亚组分析表明，使用Cox模型统计方法的研究中的关联（HR 2.76，95%CI 1.90 - 4.01，p < 0.001）比使用对数秩检验的研究中的关联更强（HR 1.41，95%CI 1.07 - 1.87，p = 0.015）。
该荟萃分析结果表明，LINE-1甲基化与CRC患者的生存期显著相关，可能是CRC预后的一个预测因素。
