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Early diagnostic potential of APC hypermethylation in esophageal cancer.

ABSTRACT: Background:The hypermethylation of APC gene is observed in various cancers, including esophageal cancer (EC). However, the association between APC methylation and the initiation and progression of EC is poorly understood. Purpose and methods:The current study systematically reviewed studies on abnormal methylation of APC in EC and quantitatively synthesized 18 studies by meta-analysis involving 1008 ECs, 570 Barrett's esophagus (BE), and 782 controls. Results:Our results showed higher methylation of APC in EC (OR = 23.33, P < 0.001) and BE (OR = 9.34, P < 0.001) than in normal controls. Whereas APC methylation in EC was similar to that in BE (P = 0.052), it was not associated with tumor stage (P = 0.204). Additionally, APC methylation was not significantly associated with overall survival (OS) and relapse-free survival (RFS) in patients with EC. The performance of APC methylation for the detection of EC and BE achieved areas under the receiver operating characteristic curves of 0.94 and 0.88, respectively. Conclusion:Our results imply that APC methylation detection is a potential diagnostic biomarker for EC and BE.

SUBMITTER: Wang B

PROVIDER: S-EPMC5798573 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Early diagnostic potential of <i>APC</i> hypermethylation in esophageal cancer.

Wang Bujiang B Song Haojun H Jiang Haizhong H Fu Yangbo Y Ding Xiaoyun X Zhou Chongchang C

Cancer management and research 20180201

<h4>Background</h4>The hypermethylation of APC gene is observed in various cancers, including esophageal cancer (EC). However, the association between APC methylation and the initiation and progression of EC is poorly understood.<h4>Purpose and methods</h4>The current study systematically reviewed studies on abnormal methylation of APC in EC and quantitatively synthesized 18 studies by meta-analysis involving 1008 ECs, 570 Barrett's esophagus (BE), and 782 controls.<h4>Results</h4>Our results sh ...[more]

PMID: 29440928

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Project description:BackgroundMutant p53 protein overexpression has been reported to induce serum antibodies against p53. Various studies assessing the diagnostic value of serum p53 antibody in patients with esophageal cancer remain controversial. This study aims to comprehensively and quantitatively summarize the potential diagnostic value of serum p53 antibody in esophageal cancer.MethodsWe systematically searched PubMed and Embase until 31st May 2012, without language restriction. Studies were assessed for quality using QUADAS (quality assessment of studies of diagnostic accuracy). Positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were pooled separately and compared with overall accuracy measures diagnostic odds ratio (DOR) and symmetric summary receiver operating characteristic (sROC). The PLR and NLR and their 95% confidence interval (CI) were calculated using a fixed effects model according to the Mantel-Haensed method and random effects model based on the work of Der Simonian and laird, respectively.ResultsFifteen studies (cases?=?1079, controls?=?2260) met the inclusion criteria for the meta-analysis. Approximately 53.33% (8/15) of the included studies were of high quality (QUADAS score?8), which were retrospective case-control studies. The summary estimates for quantitative analysis of serum p53 antibody in the diagnosis of esophageal cancer were PLR 6.95 (95% CI: 4.77-9.51), NLR 0.75 (95%CI: 0.72-0.78) and DOR 9.65 (95%CI: 7.04-13.22). However, we found significant heterogeneity between NLRs.ConclusionsThe current evidence suggests serum p53 antibody has a potential diagnostic value for esophageal cancer. However, its discrimination power is not perfect because of low sensitivity.ImpactThese results suggest that s-p53-antibody may be useful for monitoring residual tumor cells and for aiding in the selection of candidates for less invasive treatment procedures because of the high specificity of s-p53-antibody. Further studies may need to identify patterns of multiple biomarkers to further increase the power of EC detection.

Project description:BACKGROUND:Gene silencing by aberrant DNA methylation of promoter regions remains the most dominant phenomenon occurring during tumorigenesis. Improving the early diagnosis, prognosis, and recurrence prediction of colorectal cancer using noninvasive aberrant DNA methylation biomarkers has encouraging potential. The aim of this study is to characterize the DNA methylation of the promoter region of TMEM240, as well as gene expression and its effect on cell biological functions and its applications in early detection and outcome prediction. RESULTS:Highly methylated CpG sites were identified in the TMEM240 gene by Illumina methylation 450K arrays in 26 Taiwanese patient paired samples and 38 paired samples from The Cancer Genome Atlas (TCGA) colorectal cancer dataset. Transient transfection and knockdown of TMEM240 were performed to demonstrate the role of TMEM240 in colorectal cancer cells. The data showed that TMEM240 could lead to G1 cell cycle arrest, repress cancer cell proliferation, and inhibit cancer cell migration. The quantitative methylation-specific real-time polymerase chain reaction (PCR) results revealed that 87.8% (480 of 547) of the colorectal cancer tumors had hypermethylated TMEM240, and this was also found in benign tubular adenomas (55.6%). Circulating cell-free methylated TMEM240 was detected in 13 of 25 (52.0%) Taiwanese colorectal cancer patients but in fewer (28.6%) healthy controls. In 72.0% (85/118) of tissue samples, TMEM240 mRNA expression was lower in Taiwanese CRC tumor tissues than in normal colorectal tissues according to real-time reverse transcription PCR results, and this was also found in benign tubular adenomas (44.4%). The TMEM240 protein was analyzed in South Korean and Chinese CRC patient samples using immunohistochemistry. The results exhibited low protein expression in 91.7% (100/109) of tumors and 75.0% (24/32) of metastatic tumors but exhibited high expression in 75.0% (6/8) of normal colon tissues. Multivariate Cox proportional hazards regression analysis found that mRNA expression of TMEM240 was significantly associated with overall, cancer-specific, and recurrence-free survival (p = 0.012, 0.007, and 0.022, respectively). CONCLUSIONS:Alterations in TMEM240 are commonly found in Western and Asian populations and can potentially be used for early prediction and as poor prognosis and early-recurrence biomarkers in colorectal cancer.

Dataset Information

Early diagnostic potential of APC hypermethylation in esophageal cancer.

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Early diagnostic potential of <i>APC</i> hypermethylation in esophageal cancer.

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