The role of LINE-1 methylation in predicting survival among colorectal cancer patients: a meta-analysis.
BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Department of Epidemiology and Health Statistics, Zhejiang University School of Public Health, 866 Yuhangtang Road, Hangzhou, 310058, China.
Ding
D
Ye
Department of Epidemiology and Health Statistics, Zhejiang University School of Public Health, 866 Yuhangtang Road, Hangzhou, 310058, China.
Danjie
D
Jiang
Department of Public Health, Hangzhou Medical School, Hangzhou, China.
Yingjun
Y
Li
Department of Epidemiology and Health Statistics, Zhejiang University School of Public Health, 866 Yuhangtang Road, Hangzhou, 310058, China.
Mingjuan
M
Jin
Department of Epidemiology and Health Statistics, Zhejiang University School of Public Health, 866 Yuhangtang Road, Hangzhou, 310058, China. ck@zju.edu.cn.
Kun
K
Chen
D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality*; D019175:DNA Methylation; D018572:Disease-Free Survival; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D011379:Prognosis; D016016:Proportional Hazards Models
Colorectal cancer; LINE-1; Meta-analysis; Methylation; Survival