title: Loss of 5-Hydroxymethylcytosine Is an Independent Unfavorable Prognostic Factor for Esophageal Squamous Cell Carcinoma.
abstract: Ten-eleven translocation (TET) enzymes catalyze the oxidation of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine and 5-carboxylcytosine, which result in genomic DNA demethylation. It was reported that 5-hmC levels were decreased in a variety of cancers and could be regarded as an epigenetic hallmark of cancer. In the present study, 5-hmC levels were detected by immunohistochemistry (IHC) in 173 esophageal squamous cell carcinoma (ESCC) tissues and 91 corresponding adjacent non-tumor tissues; DNA dot blot assays were used to detect the 5-hmC level in another 50 pairs of ESCC tissues and adjacent non-tumor tissues. In addition, the mRNA level of TET1, TET2 and TET3 in these 50 pairs of ESCC tissues was detected by real-time PCR. The IHC and DNA dot blot results showed that 5-hmC levels were significantly lower in ESCC tissues compared with corresponding adjacent non-tumor tissues (P = 0.029). TET2 and TET3 expression was also significantly decreased in tumor tissues compared with paired non-tumor tissues (TET2, P < 0.0001; TET3, P = 0.009), and the decrease in 5-hmC was significantly associated with the downregulation of TET2 expression (r = 0.405, P = 0.004). Moreover, the loss of 5-hmC in ESCC tissues was significantly associated with poor overall survival among patients with ESCC (P = 0.043); multivariate Cox regression analysis showed that the loss of 5-hmC in ESCC tissues was an independent unfavorable prognostic indicator for patients with ESCC (HR = 1.569, P = 0.029). In conclusion, 5-hmC levels were decreased in ESCC tissues, and the loss of 5-hmC in tumor tissues was an independent unfavorable prognostic factor for patients with ESCC.
authors.affiliation: Department of Thoracic Surgery, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Xuejiao
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Thoracic Surgery, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Thoracic Surgery, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Luo
authors.affiliation: Department of Thoracic Surgery, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Susheng
authors.initials: S
authors.lastname: Shi
authors.affiliation: Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of Thoracic Surgery, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Zhaoli
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Thoracic Surgery, 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; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis
chemical_list: C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine