Abstract
The relationship between O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and clinicopathological characteristics of non-small-cell lung carcinoma (NSCLC) has remained controversial and unclear. Therefore, in this study we have undertaken a systematic review and meta-analysis of relevant studies to quantitatively investigate this association. We identified 30 eligible studies investigating 2714 NSCLC patients. The relationship between MGMT hypermethylation and NSCLC was identified based on 20 studies, including 1539 NSCLC patient tissue and 1052 normal and adjacent tissue samples (OR = 4.60, 95% CI = 3.46~6.11, p < 0.00001). MGMT methylation varied with ethnicity (caucasian: OR = 4.56, 95% CI = 2.63~7.92, p < 0.00001; asian: OR = 5.18, 95% CI = 2.03~13.22, p = 0.0006) and control style (autologous: OR = 4.44, 95% CI = 3.32~5.92, p < 0.00001; heterogeneous: OR = 9.05, 95% CI = 1.79~45.71, p = 0.008). In addition, MGMT methylation was observed to be specifically associated with NSCLC clinical stage, and not with age, sex, smoking, pathological types, and differentiation status. Also MGMT methylation did not impact NSCLC patients survival (HR = 1.32, 95% CI = 0.77~2.28, p = 0.31). Our study provided clear evidence about the association of MGMT hypermethylation with increased risk of NSCLC.
Highlights
Lung cancer has been one of the most common causes of cancer-related death in the world[1], and its incidence and mortality rates are much higher than other cancer in China[2]
Our overall pooled data demonstrated that (1) the frequency of methylguanine-DNA methyltransferase (MGMT) methylation in non-small-cell lung carcinoma (NSCLC) tissue was much higher than normal tissue samples; (2) MGMT methylation was not correlated with clinicopathological characteristics like age, sex, smoking, pathological types, and differentiated status; (3) MGMT methylation played an important role in the staging and was higher in advanced staged (III and IV) NSCLC tissue than in early staged (I and II) tissue samples; and (4) MGMT methylation could not be a prognostic factor for NSCLC prognosis
MGMT gene promoter methylation is a frequent event in NSCLC tissues showed that the MGMT gene promoter hypermethylation is associated with formation and development of NSCLC
Summary
Lung cancer has been one of the most common causes of cancer-related death in the world[1], and its incidence and mortality rates are much higher than other cancer in China[2]. Some meta-analysis studies have reported that MGMT methylation is associated with NSCLC incidence[15,16,17], but these meta-analysis were based on few studies that involved small number of diverse samples and could lead to an erroneous result They indicated quite different rates of MGMT hypermethylation from different samples, and only the samples from tumor tissue and plasma showed higher methylation than control group[15,16]. It is known that different tumor tissue specimens can have some variation, so we in our study have first summarized all published studies which included just the samples from tumor tissues of NSCLC as much as possible, and performed the systematic review and meta-analysis to quantitatively assess the association of MGMT methylation with incidence and clinical characteristics of NSCLC With this extensive and careful meta-analysis, we expect to have a better understanding of the role of MGMT methylation in NSCLC
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