CDKN2A methylation in esophageal cancer: a meta-analysis.
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ABSTRACT:
SUBMITTER: Zhou C
PROVIDER: S-EPMC5564829 | biostudies-other | 2017 Jul
REPOSITORIES: biostudies-other
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Project description:BackgroundRunt-related transcription factor 3 (RUNX3) is a member of the runt-domain family of transcription factors. Emerging evidence indicates that RUNX3 is a tumor suppressor gene in several types of human cancers including esophageal cancer. However, the association between RUNX3 promoter methylation and esophageal cancer remains unclear. Here we conducted a systematic review and meta-analysis to quantitatively evaluate the effects of RUNX3 promoter methylation on the incidence of esophageal cancer.MethodsA detailed literature search was made on Medline, Pubmed and Web of Science for related research publications written in English and/or Chinese. Methodological quality of the studies was also evaluated. The data were extracted and assessed by two reviewers independently. Analysis of pooled data were performed, the odds ratios (OR) were calculated and summarized respectively.ResultsFinal analysis of 558 patients from 9 eligible studies was performed. The result showed that RUNX3 methylation was significantly higher in esophageal cancer than in normal squamous mucosa from the proximal resection margin or esophageal benign lesions (OR = 2.85, CI = 2.01-4.05, P<0.00001). The prevalence of lymph node involvement, tumor size (T1-T2 vs T3-T4) and histological grade was significantly greater in RUNX3-negative cases (RUNX3 unmethylated groups) than in RUNX3-positive cases (OR = 0.25, CI = 0.14-0.43, P<0.00001). RUNX3 methylation was significantly higher in esophageal adenocarcinoma (EAC) than Barrett's esophagus (OR = 0.35, CI = 0.20-0.59, P<0.0001). In addition, the pooled HR for overall survival (OS) showed that decreased RUNX3 expression was associated with worse survival in esophageal cancer (HR = 4.31, 95% CI = 2.57-7.37, P<0.00001).ConclusionsThe results of this meta-analysis suggest that RUNX3 methylation is associated with an increased risk, progression as well as worse survival in esophageal cancer. RUNX3 methylation, which induces the inactivation of RUNX3 gene, plays an important role in esophageal carcinogenesis.
| S-EPMC4167998 | biostudies-literature
Project description:Reduction of cyclin-dependent kinase inhibitor 2A (CDKN2A) (p16 and p14) expression through DNA methylation has been reported in prostate cancer (PCa). This meta-analysis was conducted to assess the difference of p16 and p14 methylation between PCa and different histological types of nonmalignant controls and the correlation of p16 or p14 methylation with clinicopathological features of PCa.According to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement criteria, articles were searched in PubMed, Embase, EBSCO, Wanfang, and CNKI databases. The strength of correlation was calculated by the pooled odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs). Trial sequential analysis (TSA) was used to estimate the required population information for significant results.A total of 20 studies published from 1997 to 2017 were identified in this meta-analysis, including 1140 PCa patients and 530 cases without cancer. Only p16 methylation in PCa was significantly higher than in benign prostatic lesions (OR?=?4.72, P?=?.011), but had a similar level in PCa and adjacent tissues or high-grade prostatic intraepithelial neoplasias (HGPIN). TSA revealed that this analysis on p16 methylation is a false positive result in cancer versus benign prostatic lesions (the estimated required information size of 5116 participants). p16 methylation was not correlated with PCa in the urine and blood. Besides, p16 methylation was not linked to clinical stage, prostate-specific antigen (PSA) level, and Gleason score (GS) of patients with PCa. p14 methylation was not correlated with PCa in tissue and urine samples. No correlation was observed between p14 methylation and clinical stage or GS. CDKN2A mutation and copy number alteration were not associated with prognosis of PCa in overall survival and disease-free survival. CDKN2A expression was not correlated with the prognosis of PCa in overall survival (492 cases) (P?>?.1), while CDKN2A expression was significantly associated with a poor disease-free survival (P?<?.01).CDKN2A methylation may not be significantly associated with the development, progression of PCa. Although CDKN2A expression had an unfavorable prognosis in disease-free survival. More studies are needed to confirm our results.
| S-EPMC5895353 | biostudies-literature
Project description:Independent Component Analysis is a matrix factorization method for data dimension reduction. ICA has been widely applied for the analysis of transcriptomic data for blind separation of biological, environmental, and technical factors affecting gene expression. The study aimed to analyze the publicly available esophageal cancer data using the ICA for identification and comprehensive analysis of reproducible signaling pathways and molecular signatures involved in this cancer type. In this study, four independent esophageal cancer transcriptomic datasets from GEO databases were used. A bioinformatics tool « BiODICA-Independent Component Analysis of Big Omics Data» was applied to compute independent components (ICs). Gene Set Enrichment Analysis (GSEA) and ToppGene uncovered the most significantly enriched pathways. Construction and visualization of gene networks and graphs were performed using the Cytoscape, and HPRD database. The correlation graph between decompositions into 30 ICs was built with absolute correlation values exceeding 0.3. Clusters of components-pseudocliques were observed in the structure of the correlation graph. The top 1,000 most contributing genes of each ICs in the pseudocliques were mapped to the PPI network to construct associated signaling pathways. Some cliques were composed of densely interconnected nodes and included components common to most cancer types (such as cell cycle and extracellular matrix signals), while others were specific to EC. The results of this investigation may reveal potential biomarkers of esophageal carcinogenesis, functional subsystems dysregulated in the tumor cells, and be helpful in predicting the early development of a tumor.
| S-EPMC8594933 | biostudies-literature
Project description:BACKGROUND:Concurrent chemoradiotherapy is a standard treatment for local advanced esophageal cancer, but the outcomes are controversial. Our goals were to compare the therapeutic effects of concurrent chemoradiotherapy and radiotherapy alone in local advanced esophageal cancer using meta-analysis. METHODS:MEDLINE, EMBASE and the Cochrane library were searched for studies comparing chemoradiotherapy with radiotherapy alone for advanced esophageal cancer. Only randomized controlled trials were included, and extracted data were analyzed with Review Manager Version 5.2. The pooled relative risks (RR) and their 95% confidence intervals (CI) were calculated for statistical analysis. RESULTS:Nine studies were included. Of 1,135 cases, 612 received concurrent chemoradiotherapy and 523 were treated with radiotherapy alone. The overall response rate (complete remission and partial remission) was 93.4% for concurrent chemoradiotherapy and 83.7% for radiotherapy alone (P = 0.05). The RR values of 1-year, 3-year, and 5-year survival rates were 1.14 (95% CI: 1.04 - 1.24, P = 0.006), 1.66 (95% CI: 1.34 - 2.06, P < 0.001), and 2.43 (95% CI: 1.63 - 3.63, P < 0.001), respectively. The RR value of the merged occurrence rate of acute toxic effects was 2.34 (95% CI: 1.90 - 2.90, P <0.001). There was no difference in the incidence of late toxic effects, which had an RR value of 1.21 (95% CI: 0.96 - 1.54, P = 0.11). The RR level of persistence and recurrence was 0.71 (95% CI: 0.62 - 0.81, P <0.001), and for the distant metastasis rate, the RR value was 0.79 (95% CI: 0.61 - 1.02, P = 0.07). CONCLUSIONS:Concurrent chemoradiotherapy significantly improved overall survival rate, reduced the risk of persistence and recurrence, but had little effect on the primary tumor response, and increased the occurrence of acute toxic effects.
| S-EPMC4457836 | biostudies-literature
Project description:PurposeEarly detection of esophageal cancer is beneficial to the survival and prognosis of patients. Circular RNAs (circRNAs) have been shown to be a potential biomarker for cancer, which can be used for the diagnosis of esophageal cancer. However, the roles of circRNAs in the diagnosis of esophageal cancer has been controversial. The present study, therefore, is aimed at determining the diagnostic accuracy of circRNAs in esophageal cancer.MethodsRelevant researches were searched from PubMed, Embase, Cochrane Library, OVID, and ISI Web of Science online databases up to March 11, 2019. The estimation of diagnostic indicators, threshold effect, and publication bias were measured by a bivariate binomial mixed model, the Spearman correlation, and Deeks' funnel plot asymmetry test, respectively.ResultsFive studies from 4 articles were included in this meta-analysis. The pooled sensitivity, specificity, overall positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the receiver operating characteristics curve (AUC) were 0.79 (95% CI: 0.69-0.87), 0.85 (95% CI: 0.68-0.94), 5.27 (95% CI: 2.46-11.32), 0.24 (95% CI: 0.16-0.36), 21.66 (95% CI: 9.33-50.30), and 0.88 (95% CI: 0.84-0.90), respectively. The Spearman correlation coefficient was 0.60 (P = 0.285). The P value of Deeks' funnel plot was 0.81.ConclusionThe above-mentioned results suggested that circRNAs possess a relatively higher diagnostic performance in distinguishing esophageal cancer patients from healthy individuals. Therefore, they may serve as potential clinical biomarkers for esophageal cancer diagnosis.
| S-EPMC6732612 | biostudies-literature
Project description:Murine double minute 2 (MDM2) has suggested to play an important role in esophageal cancer. The association between MDM2 T309G polymorphism and esophageal cancer risk was inconclusive. To clarify the possible association, we conducted a meta-analysis. We searched in the PubMed, Embase, and Wanfang databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. A total of 6 studies with 4909 cases and controls were included based on the search criteria. The MDM2 T309G polymorphism was associated with a significantly decreased risk of esophageal cancer (OR=0.88; 95% CI, 0.81-0.96; I(2)=22%). When stratified by type of race, a significantly decreased esophageal cancer risk were observed in Asians (OR=0.85; 95% CI, 0.78-0.93; I(2)=0%). In conclusion, this meta-analysis suggested that MDM2 T309G polymorphism was associated with a significantly decreased risk of esophageal cancer.
| S-EPMC4612961 | biostudies-literature
Project description:BackgroundEsophageal cancer is a highly malignant cancer with a very poor prognosis. For resectable esophageal cancer, neoadjuvant treatment could improve the prognosis of esophageal cancer. However, current clinical neoadjuvant treatment options for esophageal cancer are still limited. The application of immunotherapy is a potentially beneficial new neoadjuvant treatment option for esophageal cancer. The objective of this meta-analysis is to evaluate the efficacy and safety of immunotherapy for the neoadjuvant treatment of esophageal cancer.MethodsWe will search Wanfang Database, SinoMed, China National Knowledge Infrastructure, Embase, Web of Science, Pubmed, and Cochrane Library for relevant articles published before July, 2021. We will also search the unpublished clinical trials of neoadjuvant immunotherapy in esophageal cancer in preprint website (such as bioRXiv and medRxiv) up to July, 2021. We will perform a meta-analysis to evaluate the efficacy and safety of neoadjuvant immunotherapy for resectable esophageal cancer. Randomized controlled trials (RCTs) will be included in this study. The risk of bias will be evaluated for each included study using the Cochrane Handbook for Systematic Reviews of Interventions. We will use RevMan 5.3 software for statistical analysis of the data.ResultsThe results of this study will provide evidence of immunotherapy using as neoadjuvant treatment for esophageal cancer. This meta-analysis will be submitted to a peer-reviewed journal seeking for publication.ConclusionThe results of this study will provide a reliable basis for clinicians and patients to formulate the best pre-surgical treatment plan for resectable esophageal cancer.Systematic review registrationINPLASY202120026.
| S-EPMC8177427 | biostudies-literature
Project description:We have investigated the frequency of methylation of several tumour suppressor genes in uveal melanoma. As the loss of one copy of chromosome 3 (monosomy 3), which is found in about half of these tumours, is tightly associated with metastatic disease, a special emphasis was laid on genes located on this chromosome, including the fragile histidine triad (FHIT), von Hippel-Lindau (VHL), beta-catenin (CTNNB1), activated leukocyte cell adhesion molecule (ALCAM) and retinoic acid receptor-beta2 (RARB) genes. In addition, the methylation patterns of the CpG-rich regions 5' of the E-cadherin (CDH1), p16/cyclin-dependent kinase inhibitor 2 A (CDKN2A) and retinoblastoma (RB1) genes were analysed by bisulphite genomic sequencing or methylation-specific PCR (MSP). Furthermore, the SNRPN and D15S63 loci, which are located in the imprinted region of chromosome 15, were included in the study. Aberrant methylation was detected in nine of 40 tumours analysed: The imprinted SNRPN and D15S63 loci were hypermethylated in three tumours, all of which retained both copies of chromosome 3. Methylated RARB alleles were detected in three tumours, whereas in three other tumours CDKN2A was found to be methylated. As we did not find RARB and CDKN2A preferentially methylated in tumours with monosomy 3, which is a significant predictor of metastatic disease, we suggest that these genes may play a causative role in the formation of uveal melanoma but not in the development of metastases.
| S-EPMC2448448 | biostudies-other
Project description:The association between the rs4977756 single nucleotide polymorphism (SNP) and glioma risk has been studied, but these studies have yielded conflicting results. In order to explore this association, we performed a meta-analysis. A comprehensive literature search was performed using PubMed and EMBASE database. Six articles including 12 case-control studies in English with 12022 controls and 6871 cases were eligible for the meta-analysis. Subgroup analyses were conducted by ethnicity and source of controls. Our meta-analysis found that rs4977756 polymorphism was associated with glioma risks in homozygote, heterozygote, dominant, recessive and additive genetic models (GG versus AA: OR=1.55, 95% CI=1.42-1.69, Ph=0.996, I(2)=0.0%; AG versus AA: OR=1.20, 95% CI=1.12-1.28, Ph=0.934, I(2)=0.0%; recessive model: OR=1.39, 95% CI=1.28-1.50, Ph=0.995, I(2)=0.0%; dominant model: OR=1.29, 95% CI=1.21-1.37, Ph=0.923, I(2)=0.0%; additive model: OR=1.24, 95% CI=1.19-1.30, Ph=0.966, I(2)=0.0%). Moreover, our results suggested that CDKN2A-CDKN2B rs4977756 polymorphism was associated with a notable increased risk of glioma in Europeans. However, in Asians, we could not come to a conclusion because of lack of studies. Sensitivity analysis showed the omission of any study made no significant difference. No evidence of publication bias was produced. Our meta-analysis suggested that rs4977756 polymorphism was associated with increased risk of glioma. Moreover, additional studies should be further investigated to draw a more accurate conclusion.
| S-EPMC4694238 | biostudies-literature
Project description:Colorectal cancer is among the leading causes of cancer death worldwide. Despite numerous molecular characterizations of the phenomenon, the exact dynamics of its onset and progression remain elusive. Colorectal cancer onset has been characterized by changes in DNA methylation profiles, that, owing to the stability of their patterns, are promising candidates to shed light on the molecular events laying at the base of this phenomenon.To exploit this stability and reinforce it, we conducted a meta-analysis on publicly available DNA methylation datasets generated on: normal colorectal, adenoma (ADE) and adenocarcinoma (CRC) samples using the Illumina 450k array, in the systems medicine frame, searching for tumor gene episignatures, to produce a carefully selected list of potential drivers, markers and targets of the disease. The analysis proceeds from a differential meta-analysis of the methylation profiles using an analytical pipeline recently developed by our group [1], through network reconstruction, topological and functional analyses, to finally highlight relevant epigenomic features. Our results show that genes already highlighted for their genetic or transcriptional alteration in colorectal cancer are also differentially methylated, reinforcing -regardless of the level of cellular control- their role in the complex of alterations involved in tumorigenesis.These findings were finally validated in an independent cohort from The Cancer Genome Atlas (TCGA).
| S-EPMC5355058 | biostudies-literature