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Meta-Analysis
. 2017 Jan 3;8(1):1944-1952.
doi: 10.18632/oncotarget.13719.

Decreased 5-hydroxymethylcytosine levels correlate with cancer progression and poor survival: a systematic review and meta-analysis

Zhaoli Chen  1 , Xuejiao Shi  1 , Lanwei Guo  2 , Yuan Li  1 , Mei Luo  1 , Jie He  1
Affiliations
Meta-Analysis

Decreased 5-hydroxymethylcytosine levels correlate with cancer progression and poor survival: a systematic review and meta-analysis

Zhaoli Chen et al. Oncotarget. .

Abstract

Ten-eleven translocation (TET) enzymes catalyze the oxidation of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) and then to 5-formylcytosine (5-fC) and 5-carboxylcytosine (5-caC), resulting in genomic DNA demethylation. Decreased 5-hmC levels have been reported in a variety of cancers, and loss of 5-hmC might be considered an epigenetic hallmark of cancer. However, the prognostic value of decreased 5-hmC in cancers remain controversial. Here, a systematic review was performed by conducting an electronic search of PubMed, EMBASE, Web of Science and the Cochrane Library. Finally, ten studies with a total of 1736 patients with cancer were included in the present study. Negative/low 5-hmC levels were significantly associated with lymph node metastasis [OR=2.20, 95% CI=1.23-3.96, P=0.008] and advanced TNM stage [OR=2.89, 95% CI=1.21-6.92, P=0.017]. More importantly, negative/low 5-hmC levels were significantly associated with poor prognosis of cancer patients [overall survival: HR=1.76, 95% CI=1.41-2.11, P < 0.001; disease free survival: HR=1.28, 95% CI=0.60-1.96, P < 0.001]. The results of this meta-analysis indicate that decreased 5-hmC levels are an indicator of poor survival of cancer patients. Given variability related to ethnicity, cancer types and detection methods, additional well-designed studies with larger sample sizes are required to further confirm our findings.

Keywords: 5-hydroxymethylcytosine; cancer staging; disease-free survival; meta-analysis; overall survival.

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Conflict of interest statement

CONFLICTS OF INTEREST

No potential conflicts of interest are disclosed.

Figures

Figure 1
Figure 1. Flow diagram of the selection process
Figure 2
Figure 2. Correlation of 5-hmC levels and cancer stages
A. Forest plots of the association between negative/low 5-hmC levels and lymph node metastasis (positive vs negative). B. Forest plots of the association between negative/low 5-hmC levels and TNM stage (III/IV stage vs I/II stage). C. Forest plots of the association between negative/low 5-hmC levels and histological differentiation grade (poor vs well/moderate). The squares and horizontal lines correspond to the study-specific OR and 95% CI, respectively. The area of the squares reflects the weight (inverse of the variance). The diamond represents the summary OR and 95% CI.
Figure 3
Figure 3. Prognostic value of negative/low 5-hmC levels in patients with cancer
A. Meta-analysis of the association between negative/low 5-hmC levels and overall survival in various cancers. B. Meta-analysis of the association between negative/low 5-hmC levels and disease-free survival in various cancers.
Figure 4
Figure 4. Stratified analyses of the association between 5-hmC levels and lymph node metastasis A., TNM stage B., and histological differentiation grade C. were performed by detection methods
Figure 5
Figure 5. The Begg's funnel plots and Egger's publication bias plots assessing the publication bias in analyses of the association of 5-hmC levels with lymph node metastasis A., TNM stage B., overall survival C., and disease-free survival D
See this image and copyright information in PMC

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