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Clinicopathological significance and potential drug target of RUNX3 in non-small cell lung cancer: a meta-analysis.

ABSTRACT: BACKGROUND:Emerging evidence indicates that RUNX3 is a candidate tumor suppressor in several types of human tumors, including non-small cell lung cancer (NSCLC). However, the correlation between RUNX3 hypermethylation and clinicopathological characteristics of NSCLC remains unclear. Here, we conducted a systematic review and meta-analysis to quantitatively evaluate the effects of RUNX3 hypermethylation on the incidence of NSCLC and clinicopathological characteristics. METHODS:A detailed literature search was made using Medline, Embase and Web of Science for related research publications written in English. The methodological quality of the studies was evaluated. The data were extracted and assessed independently by two reviewers. Analysis of pooled data was performed. The odds ratio (OR) and hazard ratio were calculated and summarized. RESULTS:Final analysis of 911 NSCLC patients from 13 eligible studies was performed. We observed that RUNX3 hypermethylation was significantly higher in NSCLC than in normal lung tissue; the pooled OR from seven studies including 361 NSCLC and 345 normal lung tissue (OR 7.08, confidence interval 4.12-12.17, P<0.00001). RUNX3 hypermethylation may also be associated with pathological types. The pooled OR was obtained from eleven studies including 271 squamous cell carcinoma and 389 adenocarcinoma (OR 0.41, confidence interval 0.19-0.89, P=0.02), which indicated that RUNX3 hypermethylation is significantly higher in adenocarcinoma that in squamous cell carcinoma. We did not find that RUNX3 hypermethylation was correlated with clinical stage or differentiated status. However, NSCLC patients with RUNX3 hypermethylation had a lower survival rate than those without RUNX3 hypermethylation. CONCLUSION:The results of this meta-analysis suggest that RUNX3 hypermethylation is associated with an increased risk and worse survival in NSCLC. RUNX3 hypermethylation, which induces inactivation of the RUNX3 gene, plays an important role in lung carcinogenesis and clinical outcome.

SUBMITTER: Xu L

PROVIDER: S-EPMC4461130 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Clinicopathological significance and potential drug target of RUNX3 in non-small cell lung cancer: a meta-analysis.

Xu Lijun L Lan Hongwen H Su Yushu Y Li Jun J Wan Jingwen J

Drug design, development and therapy 20150603

<h4>Background</h4>Emerging evidence indicates that RUNX3 is a candidate tumor suppressor in several types of human tumors, including non-small cell lung cancer (NSCLC). However, the correlation between RUNX3 hypermethylation and clinicopathological characteristics of NSCLC remains unclear. Here, we conducted a systematic review and meta-analysis to quantitatively evaluate the effects of RUNX3 hypermethylation on the incidence of NSCLC and clinicopathological characteristics.<h4>Methods</h4>A de ...[more]

PMID: 26082616

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Project description:BackgroundAlthough expression of long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) in tumor tissues has been assessed in several malignancies. However, the association between lncRNA MALAT-1 expression and prognosis or clinicopathological feature remains controversial. Therefore, we conducted a meta-analysis to verify whether lncRNA MALAT-1 expression was associated with prognosis or clinicopathological features in patients with non-small cell lung cancer (NSCLC).MethodsWe searched Embase, PubMed, Web of Science, Cochrane library, The Chinese National Knowledge Infrastructure, and Wanfang databases from inception to March, 1, 2020. The language restrictions were Chinese and English. The published literature on lncRNA MALAT-l expression and prognosis or clinicopathological characteristics of NSCLC patients was statistically analyzed. Combined hazard ratios (HRs), odds ratios (OR), and 95% confidence intervals (95% CIs) were used to evaluate the effects of lncRNA MALAT-l on the prognosis and clinicopathological features of NSCLC.ResultsFifteen studies with 1477 NSCLC patients were enrolled. The results showed that the elevated expression of lncRNA MALAT-l in tumor tissues was associated with shorter overall survival (OS) (HR: 2.20, 95% CI: 1.53-3.16; P = 0.000). Additionally, high lncRNA MALAT-l expression was also significantly associated with gender (OR: 0.69, 95% CI: 0.51-0.93; P = 0.014), tumor size (OR: 1.87, 95% CI:1.13-3.09; P = 0.016), lymph node metastasis (LNM) (OR: 2.87, 95% CI:1.05-7.83, P = 0.04), tumor differentiation (OR: 1.60, 95% CI:1.17-2.20; P = 0.003), and tumor-node-metastasis (TNM) stage (OR: 0.42, 95% CI: 0.25-0.70; P = 0.001). There was no significant relationship between lncRNA MALAT-l expression and other clinicopathological features including age (OR: 1.03, 95% CI: 0.79-1.34; P = 0.830), number of tumors (OR: 1.02, 95% CI: 0.63-1.64; P = 0.943), vascular invasion (OR: 1.23, 95% CI: 0.50-3.05; P = 0.652), and recurrence (OR: 1.98, 95% CI: 0.67-5.85; P = 0.214).ConclusionThe overexpression of lncRNA MALAT-l in NSCLC tissues was correlated with OS, gender, tumor size, LNM, tumor differentiation, and TNM stage. Thus, lncRNA MALAT-l may serve as a prognostic factor for NSCLC.

Project description:BackgroundVimentin is a member of the intermediate filament proteins and a canonical marker of the epithelial-mesenchymal transition (EMT), which is pivotal in tumorigenesis, metastasis and invasion in non-small cell lung cancer (NSCLC). The current meta-analysis aimed to investigate the associations between vimentin and prognosis and progression in NSCLC.MethodsDatabases with literature published in English, including PubMed, Web of Science, Embase, Science Direct, Wiley Online Library, Ovid, Cochrane Central Register of Controlled Trials, LILACS and Google Scholar, and the CNKI, VIP, CBM and WanFang databases in Chinese were used for the literature search. The key terms included (1) 'vimentin' OR 'vim' OR 'vmt' OR 'vm' OR 'hel113' OR 'ctrct30' and (2) 'pulmon*' OR 'lung' OR 'alveolar' and (3) 'cancer' OR 'carcinoma' OR 'tumor' OR 'adenocarcinoma' OR 'squamous' OR 'neoplas*' OR 'malignan*'. The data were combined by random effect model and the H value and I2 were used to assess the heterogeneity. All the meta-analysis was conducted using Stata 12.0.ResultsThirty-two qualified studies (4118 cases) were included in the current meta-analysis. Twelve studies with 1750 patients were included to assess the significance of vimentin in the overall survival (OS) of NSCLC; the pooled hazard ratio (HR) was 1.831 (confidence interval (CI): 1.315-2.550, P<0.001) in the univariate analysis and 1.266 (CI: 0.906-1.768, P = 0.167) in the multivariate analysis. Four studies with 988 cases were applicable to determine the significance of vimentin in the disease-free survival (DFS) of NSCLC; the pooled HR of the DFS was 1.224 (CI: 0.921-1.628, P = 0.164) in the univariate analysis and 1.254 (CI: 0.985-1.956, P = 0.067) in the multivariate analysis. Regarding the relationships between vimentin and clinicopathological factors, the pooled odds ratio (OR) with 3406 NSCLCs indicated that up-regulated vimentin was associated with smoking (OR = 1.359, CI: 1.098-1.683, P = 0.004), poor differentiation (OR = 2.133, CI: 1.664-2.735, P<0.001), an advanced TNM stage (OR = 3.275, CI: 1.987-5.397, P<0.001), vascular invasion (OR = 3.492, CI: 1.063-11.472, P = 0.039), lymph node metastasis (OR = 2.628, CI: 1.857-3.718, P<0.001), recurrence (OR = 1.631, CI: 1.052-2.528, P = 0.029) and pleural invasion (OR = 2.346, CI: 1.397-3.941, P = 0.001). There was no significant correlation between vimentin and age, gender, diameter, T stage, distant metastasis, or marginal invasion (P>0.05).ConclusionAn overexpression of vimentin may predict the progression and an unfavorable survival of NSCLC. Vimentin may represent a helpful biomarker and a potential target for the treatment strategies of NSCLC. Additional, prospective studies with large samples are necessary to confirm the significance of vimentin in NSCLC.

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Clinicopathological significance and potential drug target of RUNX3 in non-small cell lung cancer: a meta-analysis.

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Clinicopathological significance and potential drug target of RUNX3 in non-small cell lung cancer: a meta-analysis.

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