RGD Reference Report - Loss of 5-Hydroxymethylcytosine Is an Independent Unfavorable Prognostic Factor for Esophageal Squamous Cell Carcinoma. - Rat Genome Database

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Loss of 5-Hydroxymethylcytosine Is an Independent Unfavorable Prognostic Factor for Esophageal Squamous Cell Carcinoma.

Authors: Shi, Xuejiao  Yu, Yue  Luo, Mei  Zhang, Zhirong  Shi, Susheng  Feng, Xiaoli  Chen, Zhaoli  He, Jie 
Citation: Shi X, etal., PLoS One. 2016 Apr 6;11(4):e0153100. doi: 10.1371/journal.pone.0153100. eCollection 2016.
RGD ID: 150429668
Pubmed: PMID:27050164   (View Abstract at PubMed)
PMCID: PMC4822830   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0153100   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
esophagus squamous cell carcinoma  IEP 150429668associated with Lymphatic Metastasis and mRNA:decreased expression:esophagus squamous epithelium (human)RGD 
esophagus squamous cell carcinoma  IEP 150429668mRNA:decreased expression:esophagus squamous epithelium (human)RGD 
esophagus squamous cell carcinoma  ISOTET2 (Homo sapiens)150429668; 150429668associated with Lymphatic Metastasis and mRNA:decreased expression:esophagus squamous epithelium (human)RGD 
esophagus squamous cell carcinoma  ISOTET3 (Homo sapiens)150429668; 150429668mRNA:decreased expression:esophagus squamous epithelium (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Tet2  (tet methylcytosine dioxygenase 2)
Tet3  (tet methylcytosine dioxygenase 3)

Genes (Mus musculus)
Tet2  (tet methylcytosine dioxygenase 2)
Tet3  (tet methylcytosine dioxygenase 3)

Genes (Homo sapiens)
TET2  (tet methylcytosine dioxygenase 2)
TET3  (tet methylcytosine dioxygenase 3)


Additional Information