Evaluation of TET Family Gene Expression and 5-Hydroxymethylcytosine as Potential Epigenetic Markers in Non-small Cell Lung Cancer

Abstract

Background/Aim: DNA methylation is the most studied epigenetic modification in cancer. Ten-eleven translocation enzymes (TET) catalyze the oxidation of 5methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) in the DNA. In the current research, we aimed to evaluate the role of 5-hmC and TET enzymes in non-small cell lung cancer (NSCLC) patients and their possible association with outcomes. Patients and Methods: ELISA was used to measure the 5-hmC levels in genomic DNA and qRT-PCR was used to evaluate TET1, TET2, and TET3 mRNAs expression levels in NSCLC tissues and their paired normal controls. Results: The levels of 5-hmC were significantly lower in NSCLC tissues than in normal tissues, with a mean ±SD of 0.28±0.37 vs. 1. 84±0.58, respectively (t=22.77, p<0.0001), and this reduction was correlated with adverse clinical features. In addition, all TET genes were significantly down-regulated in NSCLC tissues in comparison to their matched normal tissues. The mean±SD level of p<0.0001), TET2-mRNA level in NSCLC was 5.25±2.78 vs. 9.52±1.01 in normal tissues (t=14.48, p<0.0001), p<0.0001). Downregulation of TET genes was correlated with poor clinical features. Conclusion: 5-HmC levels as well as TET1, TET2, and TET3 mRNA levels were reduced in NSCLC tissues. The reduced levels of 5-hmC and TET mRNAs were associated with adverse clinical features, suggesting that the level of 5-hmC may serve as a valuable prognostic biomarker for NSCLC.

Correlation of DNA methylation of DNMT3A and TET2 with oral squamous cell carcinoma

“…TET2 plays a vital role in various in ammatory conditions by regulating the immune response [16] and expressions of signaling networks and effectors during the initiation and regression of in ammation [17][18][19]. Simultaneously, TET2 mutations occur in human solid tumors, and a reduced TET2 protein expression is prevalent in several types of cancers [20][21][22][23][24][25].…”