Ciesielski Piotr, Jóźwiak Paweł, Wójcik-Krowiranda Katarzyna, Forma Ewa, Cwonda Łukasz, Szczepaniec Sylwia, Bieńkiewicz Andrzej, Bryś Magdalena, Krześlak Anna
1 Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Łódź, Poland.
2 Clinical Division of Gynecological Oncology, Medical University of Lodz, Łódź, Poland.
Tumour Biol. 2017 Mar;39(3):1010428317695017. doi: 10.1177/1010428317695017.
Ten-eleven translocation proteins are α-ketoglutarate-dependent dioxygenases involved in the conversion of 5-methylcytosines (5-mC) to 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine, and 5-carboxylcytosine that play a significant role in DNA demethylation. Deregulation of TET genes expression and changes in the level of 5-hmC are thought to be associated with the onset and progression of several types of cancer, but there are no such data related to endometrial cancer. The aim of the work was to investigate the messenger RNA expression levels of TET1, TET2, and TET3 in relation to clinicopathological characteristics of endometrial cancer as well as the correlation between expression of TET genes and the level of 5-hmC/5-mC. The prognostic significance of TETs expression for overall survival was established. We found that TET1 and TET2 messenger RNA expression was lower and TET3 was higher in cancers compared to normal tissues. Positive correlation between 5-hmC and the relative expression of TET1 and TET2 was found, but no correlation was observed in the case of TET3. Decreased expression of TET1 and TET2 was significantly associated with increased lymph node metastasis and International Federation of Gynecology and Obstetrics stage. Kaplan-Meier analysis indicated that low TET1 expression predicted poor overall survival (p = 0.038). Multivariate analysis identified the TET1 expression in endometrial cancer as an independent prognostic factor. Our results suggest that decreased expression of TET1 correlates with tumor progression and may serve as a potential prognostic biomarker in endometrial cancer.
10-11易位蛋白是依赖α-酮戊二酸的双加氧酶，参与5-甲基胞嘧啶（5-mC）向5-羟甲基胞嘧啶（5-hmC）、5-甲酰基胞嘧啶和5-羧基胞嘧啶的转化，这些转化在DNA去甲基化中起重要作用。TET基因表达失调和5-hmC水平变化被认为与多种癌症的发生和进展有关，但尚无与子宫内膜癌相关的数据。这项工作的目的是研究TET1、TET2和TET3的信使RNA表达水平与子宫内膜癌临床病理特征的关系，以及TET基因表达与5-hmC/5-mC水平之间的相关性。确定了TETs表达对总生存期的预后意义。我们发现，与正常组织相比，癌症中TET1和TET2信使RNA表达较低，而TET3表达较高。发现5-hmC与TET1和TET2的相对表达呈正相关，但TET3未观察到相关性。TET1和TET2表达降低与淋巴结转移增加和国际妇产科联合会分期显著相关。Kaplan-Meier分析表明，TET1低表达预示总生存期较差（p = 0.038）。多变量分析确定子宫内膜癌中TET1表达为独立的预后因素。我们的结果表明，TET1表达降低与肿瘤进展相关，可能作为子宫内膜癌潜在的预后生物标志物。
