Expression of methylation-related genes is associated with overall survival in patients with non-small cell lung cancer

Abstract

The abnormality of DNA methylation is involved in tumour progression, and thus has a modulating effect on clinical outcome of cancer patients. In this study, we measured the mRNA expression levels of three methylation-regulating genes (DNMT1, DNMT3b, and MBD2) in 148 tumour samples from patients with non-small cell lung cancer (NSCLC) using quantitative real-time polymerase chain reaction and then determined their prognostic values. Our data showed that the high level of DNMT1 expression was significantly associated with an increased risk of death in all NSCLC patients (hazard ratio (HR), 1.74; 95% confidence interval (95% CI), 1.04 -2.90). However, the high level of DNMT3b expression was significantly associated with poor prognosis only in young patients (o65 years). The high level of MBD2 expression had a significantly reduced risk for death only in male patients and in squamous cell lung carcinoma (SQLC) patients. All three combination groups with DNMT1 and DNMT3b, DNMT1 and MBD2 or DNMT3b and MBD2 revealed significant combined effects in male patients and SQLC patients. Our results suggest that DNMT1, DNMT3b, and MBD2 may play important roles in modulating NSCLC patient survival and thus be useful for identifying NSCLC patients who would benefit most from aggressive therapy.

Overexpression of DNA methyltransferase 1 as a negative independent prognostic factor in primary gastrointestinal diffuse large B-cell lymphoma treated with CHOP-like regimen and rituximab

“…The Cox regression analysis revealed that DNMT1 was an independent prognostic factor, which suggests that DNMT1 expression may be a suitable prognostic marker for patients with PGI-DLBCL. These findings are consistent with those of other previous studies (28)(29)(30)(31)(32)(33)(34)(35)(36). Although previous studies have reported that the levels of DNMT3a and DNMT3b were significantly higher in cancer patients (31,33,35,36), the present study indicated that the expression of DNMT3a and DNMT3b in PGI-DLBCL patients was markedly lower than that of the healthy controls.…”

“…Another study identified that the level of DNMT1 mRNA was significantly higher in gastric cancer patients with methylated Runx3, compared with those with unmethylated Runx3 (30). Furthermore, increased expression of DNMT1 and DNMT3b have been detected in the tumor tissues of patients with lung cancer, and were also associated with poorer prognoses (31)(32)(33)(34). In a study concerning pancreatic cancer patients, those with a higher DNMT1 expression exhibited a lower overall survival rate (35).…”

“…DNMT1 mediates maintenance DNA methylation and DNMT3a and DNMT3b are responsible for de novo methylation (9). Previous studies have revealed that DNMT1 and DNMT3b overexpression is associated with unfavorable prognoses in a number of human cancers, including breast and hepatocellular carcinomas, lung cancers, acute myeloid leukemia and epithelial ovarian cancer (11)(12)(13)(14)(15)(16)(17).…”

UHRF1‐mediated tumor suppressor gene inactivation in nonsmall cell lung cancer

“…The overexpression of DNMT3B correlated with poor survival in our NSCLC set, and this is in agreement with a previous study demonstrating prognostic significance of DNMT3B expression but only in younger patients aged <65 years. 51 The potential clinical implementation of these observations should be further investigated.…”

Epigenetic and Transcriptional Changes Which Follow Epstein-Barr Virus Infection of Germinal Center B Cells and Their Relevance to the Pathogenesis of Hodgkin's Lymphoma

“…Whereas DNMT1 has a preference for hemimethylated DNA and is involved in the maintenance of methylation, DNMT3A and DNMT3B function as de novo methyltransferases. Increased expression of one or more of the DNMT has been reported at a number of sites of cancer and has been shown to be an adverse prognostic factor (1,23,39).…”