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Meta-Analysis
. 2016 Feb 10;11(2):e0149088.
doi: 10.1371/journal.pone.0149088. eCollection 2016.

Distinguishing Lung Adenocarcinoma from Lung Squamous Cell Carcinoma by Two Hypomethylated and Three Hypermethylated Genes: A Meta-Analysis

Affiliations
Meta-Analysis

Distinguishing Lung Adenocarcinoma from Lung Squamous Cell Carcinoma by Two Hypomethylated and Three Hypermethylated Genes: A Meta-Analysis

Tao Huang et al. PLoS One. .

Abstract

Significant differences in the aberrant methylation of genes exist among various histological types of non-small cell lung cancer (NSCLC), which includes adenocarcinoma (AC) and squamous cell carcinoma (SCC). Different chemotherapeutic regimens should be administered to the two NSCLC subtypes due to their unique genetic and epigenetic profiles. The purpose of this meta-analysis was to generate a list of differentially methylated genes between AC and SCC. Our meta-analysis encompassed 151 studies on 108 genes among 12946 AC and 10243 SCC patients. Our results showed two hypomethylated genes (CDKN2A and MGMT) and three hypermethylated genes (CDH13, RUNX3 and APC) in ACs compared with SCCs. In addition, our results showed that the pooled specificity and sensitivity values of CDH13 and APC were higher than those of CDKN2A, MGMT and RUNX3. Our findings might provide an alternative method to distinguish between the two NSCLC subtypes.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Flow diagram.
The flow diagram of the stepwise selection from relevant studies.
Fig 2
Fig 2. Forest and funnel plots of CDKN2A and MGMT.
The forest plots of CDKN2A and MGMT displayed the effect size and 95% CIs for the included studies. Funnel plots suggested no publication bias in the meta-analyses of CDKN2A and MGMT genes. Our results showed that the total ORs for CDKN2A and MGMT were less than1, which demonstrated the methylation of CDKN2A and MGMT in AC were relatively higher than in SCC. Funnel plots of meta-analyses of CDH13, RUNX3 and APC demonstrated no publication biases in the included studies. In addition, M-H denotes Mantel-Haenszel statistical method to calculate the combined odds ratios (ORs) and the corresponding 95% confidence intervals (95% CIs). Weight denotes the weighted average of the intervention effect estimated in each study. SE denotes standard errors.
Fig 3
Fig 3. Forest and funnel plots of CDH13, RUNX3 and APC.
The forest plots of CDH13, RUNX3 and APC displayed the effect size and 95% CIs for the included studies. Our results showed that the total ORs of CDH13, RUNX3 and APC demonstrated that the methylation of CDH13, RUNX3 and APC in AC were significantly more frequent than in SCC. Funnel plots of meta-analyses of CDH13, RUNX3 and APC demonstrated no publication biases in the included studies. The details of abbreviations (M-H, ORs, CIs, and SE) and weight were shown in the legends of Fig 2.

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