Meta-analysis of the Association between RASSF1A Gene Promoter Methylation and Non-small Cell Lung Cancer

Background and objective The CpG island aberrant promoter methylation in the tumor suppressor gene region plays an important role in the process of tumorigenesis. Relevant evidence shows that the promoter methylation of RAS association domain family 1A (RASSF1A) gene, a tumor suppressor gene, has a close relationship with non-small cell lung cancer (NSCLC) development; therefore, RASSF1A may be a potential NSCLC biomarker. This paper discussed and summarized the relationship between RASSF1A gene promoter methylation frequency and NSCLC through meta-analysis. Methods By searching Medline, EMBASE, CNKI, and Wanfang database, we selected and collected the published articles regarding RASSF1A gene promoter methylation and NSCLC risk according to the marked inclusion and exclusion criteria. Through meta-analysis, combined odds ratio (OR) and 95% confidence interval (CI) data were used to analyze the RASSF1A gene promoter methylation and NSCLC relationship. Results A total of 23 articles were utilized in this study. Results indicated that the RASSF1A gene promoter methylation rate was 41.50% (95%CI: 34%-49%) in NSCLC tissue and was 5.58% (95%CI: 2%-9%) for the control group. Compared with normal lung tissue, RASSF1A methylation frequency in tumor tissue was significantly higher than that of the control group (OR=8.72, 95%CI: 4.88-15.58, P<0.05). Subgroup analysis showed that the RASSF1A gene promoter methylation rate of tumor tissue was higher than that of plasma group (OR=10.99, 95%CI: 2.48-48.68) and normal control tissue group (OR=8.74, 95%CI: 4.39-17.41). Conclusion The rate of RASSF1A promoter gene methylation in NSCLC patient tissue samples was higher than that of normal lung samples, whereas the rate of RASSF1A promoter gene methylation in the tissue has more significant effect on lung cancer occurrence. This finding indicates that RASSF1A gene promoter methylation could be used as an NSCLC biomarker and was involved in NSCLC carcinogenic effects

A Meta-analysis of Association between MGMT Gene Promoter Methylation and Non-small Cell Lung Cancer

Backgroud and objective DNA promoter methylation of the tumor suppressor genes was one of the key mechanism for gene silence. The aim of this study is to investigate the difference of MGMT gene promoter methylation rate in tumor tissue and autologous controls (serum, normal lung tissue and bronchial lavage fluid) in patients with non-small cell lung cancer (NSCLC). Methods The databases of Medline, EMBSE, CNKI and Wanfang were searched for selection of published articles of MGMT gene promoter methylation and non-small cell lung carcinoma risk. The pooled odds ratio (OR) and percentage of MGMT for lung cancer tissue of NSCLC patients compared with normal lung tissue, plasma and the bronchial lavage fluid were pooled. Results 15 articles of association between MGMT gene promoter methylation and non small cell lung carcinoma risk were included in this meta-analysis. The combined results demonstrated the methylation rate of MGMT in NSCLC cancer tissue was 38% (95%CI: 23%-53%). For normal lung tissue, plasma and the bronchial lavage fluid were 16% (95%CI: 5%-27%), 23% (95%CI: 10%-34%) and 39% (95%CI: 23%-55%) respectively. The OR in cancer tissue was much higher than that in normal lung tissue and plasma odds ratio (OR) 3.98 (95%CI: 2.71-5.84, P0.05). Conclusions Mehtylation rate in MGMT gene promoter of cancer tissue in NSCLC patients was much higher than that in normal lung tissue and plasma, which showed a close association between NSCLC cancer and MGMT gene promoter methylation

A Meta-Analysis of the Relationship Between <i>RARβ</i> Gene Promoter Methylation and Non-Small Cell Lung Cancer

<div><p>Background</p><p>Hypermethylation of CpG islands in tumor suppressor gene plays an important role in carcinogenesis. Many studies have demonstrated that hypermethylation in promoter region of <i>RARβ</i> gene could be found with high prevalence in tumor tissue and autologous controls such as corresponding non-tumor lung tissue, sputum and plasma of the NSCLC patients. But with the small number subjects included in the individual studie, the statistical power is limited. Accordingly, we performed this meta-analysis to further asses the relationship of methylation prevalence between the cancer tissue and atuologous controls (corresponding non-tumor lung tissue, sputum and plasma).</p><p>Methods</p><p>The published articles about <i>RARβ</i> gene promoter hypermethyltion were identified using a systematic search strategy in PubMed, EMBASE and CNKI databases. The pooled odds ratio (OR) of <i>RARβ</i> promoter methylation in lung cancer tissue versus autologous controls were calculated.</p><p>Results</p><p>Finally, eleven articles, including 1347 tumor tissue samples and 1137 autologous controls were included in this meta-analysis. The pooled odds ratio of <i>RARβ</i> promoter methylation in cancer tissue was 3.60 (95%CI: 2.46–5.27) compared to autologous controls with random-effect model. Strong and significant correlation between tumor tissue and autologous controls of <i>RARβ</i> gene promoter hypermethylation prevalence across studies (Correlation coefficient 0.53) was found.</p><p>Conclusion</p><p><i>RARβ</i> promoter methylation may play an important role in carcinogenesis of the NSCLC. With significant methylation prevalence correlation between tumor tissue and autologous of this gene, methylation detection may be a potential method for searching biomarker for NSCLC.</p></div

Begg's funnel plot for assessment of publication bias.

<p>Begg's funnel plot for assessment of publication bias.</p

The distribution of methylation rate for each included study (the paired tissue were in the same colour).

<p>The distribution of methylation rate for each included study (the paired tissue were in the same colour).</p

Flowchart of the literature search strategy (Data from some studies was used more than once).

<p>Flowchart of the literature search strategy (Data from some studies was used more than once).</p

Subgroup analysis.

<p>Subgroup analysis.</p

General characteristics of included studies.

<p>M = male; F = female; T = tumor; C = control; CNTLT =  Corresponding non-tumor lung tissues; NA = not aviable.</p

Forest plot of pooled OR for <i>RARβ</i> gene promoter methylation in cancer tissue versus autologous controls.

<p>Forest plot of pooled OR for <i>RARβ</i> gene promoter methylation in cancer tissue versus autologous controls.</p

MiR-132 Suppresses the Migration and Invasion of Lung Cancer Cells <i>via</i> Targeting the EMT Regulator ZEB2

<div><p>MicroRNAs (miRNAs) are small, non-coding RNAs which can function as oncogenes or tumor suppressor genes in human cancers. Emerging evidence reveals that deregulation of miRNAs contributes to the human non-small cell lung cancer (NSCLC). In the present study, we demonstrated that the expression levels of miR-132 were dramatically decreased in examined NSCLC cell lines and clinical NSCLC tissue samples. Then, we found that introduction of miR-132 significantly suppressed the migration and invasion of lung cancer cells in vitro, suggesting that miR-132 may be a novel tumor suppressor. Further studies indicated that the EMT-related transcription factor ZEB2 was one direct target genes of miR-132, evidenced by the direct binding of miR-132 with the 3′ untranslated region (3′ UTR) of ZEB2. Further, miR-132 could decrease the expression of ZEB2 at the levels of mRNA and protein. Notably, the EMT marker E-cadherin or vimentin, a downstream of ZEB2, was also down-regulated or up-regulated upon miR-132 treatment. Additionally, over-expressing or silencing ZEB2 was able to elevate or inhibit the migration and invasion of lung cancer cells, parallel to the effect of miR-132 on the lung cancer cells. Meanwhile, knockdown of ZEB2 reversed the enhanced migration and invasion mediated by anti-miR-132. These results indicate that miR-132 suppresses the migration and invasion of NSCLC cells through targeting ZEB2 involving the EMT process. Thus, our finding provides new insight into the mechanism of NSCLC progression. Therapeutically, miR-132 may serve as a potential target in the treatment of human lung cancer.</p></div