title: Decreased 5-hydroxymethylcytosine levels correlate with cancer progression and poor survival: a systematic review and meta-analysis.
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.
authors.affiliation: Department of Thoracic Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Zhaoli
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Thoracic Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Xuejiao
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Cancer Epidemiology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Henan Office for Cancer Control and Research, Zhengzhou, China.
authors.forename: Lanwei
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Thoracic Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Luo
authors.affiliation: Department of Thoracic Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: He
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D003596:Cytosine / Q000031:analogs & derivatives / Q000737:chemistry; D019175:DNA Methylation / Q000235:genetics*; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics; D009369:Neoplasms / Q000235:genetics* / Q000401:mortality*; D011379:Prognosis
chemical_list: C560974:5-carboxylcytosine; C560973:5-formylcytosine; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine
keywords: 5-hydroxymethylcytosine; cancer staging; disease-free survival; meta-analysis; overall survival