The role of the ßKlotho gene in uterine endometrial cancer.

OBJECTIVES: Endometrial cancer is the most common cancer of the female genital organs in developed countries, accounting for approximately 50% of all gynecological cancers. The Klotho gene was discovered in 1997 as an anti-aging gene that, when overexpressed, may extend the lifespan, but when disrupted, may be a factor responsible for premature aging syndrome. The aim of the study is to assess the relationship between the clinical and pathological features of endometrial cancer and ßKlotho gene expression. MATERIAL AND METHODS: The expression of ßKlotho gene was studied in 138 cases of endometrioid endometrial carcinoma specimens using Real Time PCR reaction in RNA isolated tissue samples by commercial tests. The expression profile was correlated with the clinicopathological characteristics of endometrial carcinoma. The chi-square independence test and Fisher's test for four-field tables were used to assess the statistical significance of the observed relationships. RESULTS: Significant relationships were found between ßKlotho gene expression and FIGO clinical stage, the degree of histological differentiation and the presence of metastases in the lymph nodes. Higher levels of gene expression correlate with lower degrees of clinical staging according to FIGO, the presence of highly-differentiated endometrial cancer (G1) and the absence of lymph node metastases. CONCLUSIONS: The ßKlotho gene expression might be involved in endometrioid endometrial cancer tumorgenesis. The ßKlotho may in future be used as an useful indicator for endometrial cancer, although further studies are needed.

Differential expression of ten-eleven translocation genes in endometrial cancers.

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.