Methylation of the DLEC1 gene correlates with poor prognosis in Japanese lung cancer patients

Abstract

Abstract. the incidence of chromosome 3p gene alterations is one of the most frequent and earliest documented events in lung cancer. this study aimed to investigate promoter methylation in the deleted in lung and esophageal cancer 1 (DLEC1) gene, as well as the p16 and CDH1 genes in Japanese lung cancer cases. the methylation status of the promoter regions of DLEC1, p16 and CDH1 was investigated using methylation-specific PCR. The findings were compared to the clinicopathological features of lung cancer. Methylation-specific PCR showed that the DLEC1 promoter region was methylated in 65 out of 116 (56%) lung cancers. Patients with DLEC1-methylated cancer were associated with a significantly worse prognosis than those with unmethylated cancer (p=0.0368; hazard ratio=1.83). the p16 methylation status correlated with squamous histology (p=0.03) and smoking status (never smoker vs. smoker; p=0.0122). Patients with p16 ummethylated cancer harbored more EGFR mutations (p=0.0071). the CDH1 promoter region was hypermethylated in 65 out of 118 (55.1%) lung cancer cases. However, the CDH1 methylation status was not associated with the clinicopathological characteristics of the lung cancer types. p16 and CDH1 methylation status did not correlate with survival in the lung cancer patients. thus, in our Japanese cohort, the methylation status of the DLEC1 gene was a marker of poor prognosis independent of stage.

DLEC1 is not silenced solely by promoter methylation in head and neck squamous cell carcinoma

“…This frequency is similar to those which have been observed in lung (Y. Zhang et al, 2010;Sasaki et al, 2010) cancer (41-56%) and renal cell carcinoma (Q. Zhang et al, 2010) (31%).…”

The Prognostic Value of Epigenetic Silencing of p16 Gene in NSCLC Patients: A Systematic Review and Meta-Analysis

“…Nine were excluded for the systematic review after full assessment (7 were lacking relevant survival data, another 2 were duplications). Of the 25 remained studies, eighteen studies were eligible for the meta-analysis [9], [12], [13], [14], [15], [18], [19], [22], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], 7 provided insufficient data for performing a quantitative aggregation [11], [17], [20], [39], [40], [41], [42].…”

“…The contribution of p16 deregulation through methylation to the carcinogenic process has been extensively studied. Moreover, bulks of observational studies evaluating its prognostic value in NSCLC have been carried out in past ten years [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22].…”

Exome-Wide Association Study Identifies Low-Frequency Coding Variants in 2p23.2 and 7p11.2 Associated with Survival of Non–Small Cell Lung Cancer Patients

“…The gene CCT6A identified by the single-variant analysis was also significant in the gene-based analysis (p ¼ 0.005), but PLB1 was not replicated in the genebased analysis. Among the 32 identified genes, period circadian clock 1 gene (PER1), deleted in lung and esophageal cancer 1 gene (DLEC1), F2R like thrombin/ trypsin receptor 3 gene (F2RL3), and patched 1 gene (PTCH1) had been associated with survival of patients with lung cancer through different mechanisms [25][26][27][28] and polo like kinase 4 (PLK4) was demonstrated to be implicated in mitotic and cancer development. 29 However, the roles of remaining genes in the progression of NSCLC were not reported before.…”