Abstract
BackgroundAberrant methylation of CpG islands acquired in tumor cells in promoter regions plays an important role in carcinogenesis. Accumulated evidence demonstrates P16INK4a gene promoter hypermethylation is involved in non-small cell lung carcinoma (NSCLC), indicating it may be a potential biomarker for this disease. The aim of this study is to evaluate the frequency of P16INK4a gene promoter methylation between cancer tissue and autologous controls by summarizing published studies.MethodsBy searching Medline, EMBSE and CNKI databases, the open published studies about P16INK4a gene promoter methylation and NSCLC were identified using a systematic search strategy. The pooled odds of P16INK4A promoter methylation in lung cancer tissue versus autologous controls were calculated by meta-analysis method.ResultsThirty-four studies, including 2 652 NSCLC patients with 5 175 samples were included in this meta-analysis. Generally, the frequency of P16INK4A promoter methylation ranged from 17% to 80% (median 44%) in the lung cancer tissue and 0 to 80% (median 15%) in the autologous controls, which indicated the methylation frequency in cancer tissue was much higher than that in autologous samples. We also find a strong and significant correlation between tumor tissue and autologous controls of P16INK4A promoter methylation frequency across studies (Correlation coefficient 0.71, 95% CI:0.51–0.83, P<0.0001). And the pooled odds ratio of P16INK4A promoter methylation in cancer tissue was 3.45 (95% CI: 2.63–4.54) compared to controls under random-effect model.ConclusionFrequency of P16INK4a promoter methylation in cancer tissue was much higher than that in autologous controls, indicating promoter methylation plays an important role in carcinogenesis of the NSCLC. Strong and significant correlation between tumor tissue and autologous samples of P16INK4A promoter methylation demonstrated a promising biomarker for NSCLC.
Highlights
Lung cancer, accounting for 13% (1.6 million) of the total cases and 18% (1.4 million) of the deaths, was the most commonly diagnosed cancer as well as the leading cause of cancer death worldwide in 2008 [1]
We find a strong and significant correlation between tumor tissue and autologous samples of P16INK4A promoter methylation across studies (Correlation coefficient 0.71, 95% CI:0.51–0.83, P,0.0001,)
The methylation frequency ranged from 6% to 74%, which showed a significant correlation of P16INK4A promoter methylation with cancer tissue (Correlation coefficient 0.72, 95% CI: 0.27–0.91, P = 0.0059, Fig 5A)
Summary
Lung cancer, accounting for 13% (1.6 million) of the total cases and 18% (1.4 million) of the deaths, was the most commonly diagnosed cancer as well as the leading cause of cancer death worldwide in 2008 [1]. Benefiting from the tobacco control, lung cancer death rate is decreasing in western developed countries. It is increasing in developing countries such as China, where smoking prevalence is still increasing [1]. Non-small cell lung cancer, accounting for 80% of primary lung carcinomas, was the most common type with a 5-year survival rate ranging from 2 to 47% for different clinical stages and histopathology [2]. Accumulated evidence demonstrates P16INK4a gene promoter hypermethylation is involved in non-small cell lung carcinoma (NSCLC), indicating it may be a potential biomarker for this disease. The aim of this study is to evaluate the frequency of P16INK4a gene promoter methylation between cancer tissue and autologous controls by summarizing published studies
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