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The clinicopathological significance of FHIT hypermethylation in non-small cell lung cancer, a meta-analysis and literature review.

ABSTRACT: Emerging evidence indicates that FHIT is a candidate tumor suppressor in non-small cell lung cancer (NSCLC). However, the correlation between FHIT hypermethylation and clinicopathological characteristics of NSCLC remains unclear. Thus, we conducted a meta-analysis to quantitatively evaluate the effects of FHIT hypermethylation on the incidence of NSCLC and clinicopathological characteristics. Final analysis of 1717 NSCLC patients from 16 eligible studies was performed. FHIT hypermethylation was found to be significantly higher in NSCLC than in normal lung tissue, the pooled OR from 8 studies including 735 NSCLC and 708 normal lung tissue, OR = 5.45, 95% CI = 2.15-13.79, p = 0.0003. FHIT hypermethylation was also correlated with sex status, smoking status, as well as pathological types. We did not find that FHIT hypermethylation was correlated with the differentiated types or clinical stages in NSCLC patients. However, patients with FHIT hypermethylation had a lower survival rate than those without, HR = 1.73, 95% CI = 1.10-2.71, p = 0.02. The results of this meta-analysis suggest that FHIT hypermethylation is associated with an increased risk and worsen survival in NSCLC patients. FHIT hypermethylation, which induces the inactivation of FHIT gene, plays an important role in the carcinogenesis and clinical outcome and may serve as a potential drug target of NSCLC.

SUBMITTER: Yan W

PROVIDER: S-EPMC4726317 | biostudies-other | 2016 Jan

REPOSITORIES: biostudies-other

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Project description:BackgroundEmerging 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.MethodsA 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.ResultsFinal 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.ConclusionThe 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.

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.

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The clinicopathological significance of FHIT hypermethylation in non-small cell lung cancer, a meta-analysis and literature review.

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