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 and Jie He 1 1 Department of Thoracic Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China 2 Department of Cancer Epidemiology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Henan Office for Cancer Control and Research, Zhengzhou, China * These authors have contributed equally to this work Correspondence to: Jie He, email: // Keywords : 5-hydroxymethylcytosine; cancer staging; overall survival; disease-free survival; meta-analysis Received : April 10, 2016 Accepted : September 14, 2016 Published : November 30, 2016 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.