Aberrant Methylation of MEG3 Functions as a Potential Plasma-Based Biomarker for Cervical Cancer

Zhang, Jun; Yao, Tingting; Lin, Zhongqiu; Gao, Yali

doi:10.1038/s41598-017-06502-7

Cited by 55 publications

(47 citation statements)

References 22 publications

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“…36 Though little research describes aberrant methylation of MEG3, hypermethylation has been implicated as a potential biomarker in cervical cancer. 37 When estimating time-to-regression at a single follow-up visit, increased methylation at the Kv DMR also decreased the probability of regression relative to women who had lower levels of methylation. The Kv DMR is maternally methylated, comprised of the imprint control region IC2 located at Chr11p15.5, which regulates at least 11 imprinted genes.…”

Section: Discussionmentioning

confidence: 99%

DNA methylation of imprinted gene control regions in the regression of low‐grade cervical lesions

Gomih

Smith

North

et al. 2018

Intl Journal of Cancer

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The role of host epigenetic mechanisms in the natural history of low-grade cervical intraepithelial neoplasia (CIN1) is not well characterized. We explored differential methylation of imprinted gene regulatory regions as predictors of the risk of CIN1 regression. A total of 164 patients with CIN1 were recruited from 10 Duke University clinics for the CIN Cohort Study. Participants had colposcopies at enrollment and up to five follow-up visits over 3 years. DNA was extracted from exfoliated cervical cells for methylation quantitation at CpG (cytosine-phosphate-guanine) sites and human papillomavirus (HPV) genotyping. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression to quantify the effect of methylation on CIN1 regression over two consecutive visits, compared to non-regression (persistent CIN1; progression to CIN2+; or CIN1 regression at a single time-point), adjusting for age, race, high-risk HPV (hrHPV), parity, oral contraceptive and smoking status. Median participant age was 26.6 years (range: 21.0-64.4 years), 39% were African-American, and 11% were current smokers. Most participants were hrHPV-positive at enrollment (80.5%). Over one-third of cases regressed (n = 53, 35.1%). Median time-to-regression was 12.6 months (range: 4.5-24.0 months). Probability of CIN1 regression was negatively correlated with methylation at IGF2AS CpG 5 (HR = 0.41; 95% CI = 0.23-0.77) and PEG10 DMR (HR = 0.80; 95% CI = 0.65-0.98). Altered methylation of imprinted IGF2AS and PEG10 DMRs may play a role in the natural history of CIN1. If confirmed in larger studies, further research on imprinted gene DMR methylation is warranted to determine its efficacy as a biomarker for cervical cancer screening.

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Section: Discussionmentioning

confidence: 99%

DNA methylation of imprinted gene control regions in the regression of low‐grade cervical lesions

Gomih

Smith

North

et al. 2018

Intl Journal of Cancer

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“…Among these key lncRNA, several studies have reported that lncRNA MEG3 played crucial roles in the development of various cancers, such as: non-small cell lung cancer, cervical cancer, colorectal cancer, esophageal cancer. [39][40][41][42][43] The lncRNA MEG3 had effects to suppress cervical cancer by regulation of PI3K/AKT/Bcl-2/Bax/P21 and PI3K/AKT/ MMP-2/9 signaling pathways. However, only two studies demonstrated that lncRNA ADAMTS9-AS2 was associated with development of gliomas, 44 and colorectal cancer.…”

Section: Discussionmentioning

confidence: 99%

Reconstruction and analysis of the aberrant lncRNA‐miRNA‐mRNA network based on competitive endogenous RNA in CESC

Song

Jiang

et al. 2018

J of Cellular Biochemistry

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A growing body of studies has demonstrated that long non‐coding RNA (lncRNA) are regarded as the primary section of the ceRNA network. This is thought to be the case owing to its regulation of protein‐coding gene expression by functioning as miRNA sponges. However, functional roles and regulatory mechanisms of lncRNA‐mediated ceRNA in cervical squamous cell carcinoma (CESC), as well as their use for potential prediction of CESC prognosis, remains unknown. The aberrant expression profiles of mRNA, lncRNA, and miRNA of 306 cervical squamous cancer tissues and three adjacent cervical tissues were obtained from the TCGA database. A lncRNA‐mRNA‐miRNA ceRNA network in CESC was constructed. Meanwhile, Gene Ontology (GO) and KEGG pathway analysis were performed using Cytoscape plug‐in BinGo and DAVID database. We identified a total of 493 lncRNA, 70 miRNA, and 1921 mRNA as differentially expressed profiles. An aberrant lncRNA‐mRNA‐miRNA ceRNA network was constructed in CESC, it was composed of 50 DElncRNA, 18 DEmiRNA, and 81 DEmRNA. According to the overall survival analysis, 3 out of 50 lncRNA, 10 out of 81 mRNA, and 1 out of 18 miRNA functioned as prognostic biomarkers for patients with CESC (P value < 0.05). We extracted the sub‐network in the ceRNA network and found that two novel lncRNA were recognized as key genes. These included lncRNA MEG3 and lncRNA ADAMTS9‐AS2. The present study provides a new insight into a better understanding of the lncRNA‐related ceRNA network in CESC, and the novel recognized ceRNA network will help us to improve our understanding of lncRNA‐mediated ceRNA regulatory mechanisms in the pathogenesis of CESC.

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“…Ten of 15 included studies had selected circulating HPV DNA as a detected gene target. Other gene targets had higher sensitivity but lower specificity, including SIM1 methylation [26], MEG3 methylation [28], Bmi-1 [29], miR-21 [30], and hsa-miR-92a [31].…”

Section: Discussionmentioning

confidence: 99%

“…Two studies [10,24] increased the risk of bias owing to a lack of patient selection. Four studies [25][26][27][28] did not mention the use of a blinding method or reference standard, which may have resulted in an unknown risk of bias in the meta-analysis.…”

Section: Quality Assessmentmentioning

confidence: 99%

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Diagnostic value of circulating tumor DNA as an effective biomarker in cervical cancer: a meta-analysis

C²,

Qiu

et al. 2019

Preprint

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The applications of liquid biopsy have attracted much attention in biomedical research in recent years. Circulating cell-free DNA (cfDNA) in the serum may serve as a unique tumor marker in various types of cancer. Circulating tumor DNA (ctDNA) is a type of serum cfDNA found in patients with cancer and contains abundant information regarding tumor characteristics, highlighting its potential diagnostic value in the clinical setting. However, the diagnostic value of cfDNA as a biomarker in cervical cancer remains unclear. Here, we performed a metaanalysis to evaluate the applications of ctDNA as a biomarker in cervical cancer. A systematic literature search was performed using PubMed, Embase, and WANFANG MED ONLINE databases up to March 18, 2019. All literature was analyzed using Meta Disc 1.4 and STATA 14.0 software. Diagnostic measures of accuracy of ctDNA in cervical cancer were pooled and 2investigated. Fifteen studies comprising 1109 patients with cervical cancer met our inclusion criteria and were subjected to analysis. The pooled sensitivity and specificity were 0.52 (95% confidence interval [CI], 0.33-0.71) and 0.97 (95% CI, 0.91-0.99), respectively. The pooled positive likelihood ratio and negative likelihood ratio were 16.0 (95% CI, 5.5-46.4) and 0.50 (95% CI, 0.33-0.75), respectively. The diagnostic odds ratio was 32 (95% CI, 10-108), and the area under the summary receiver operating characteristic curve was 0.92 (95% CI, 0.90-0.94). There was no significant publication bias observed. In the included studies, ctDNA showed clear diagnostic value for diagnosing and monitoring cervical cancer. Our metaanalysis suggested that detection of human papilloma virus ctDNA in patients with cervical cancer could be used as a noninvasive early dynamic biomarker of tumors, with high specificity and moderate sensitivity. Further large-scale prospective studies are required to validate the factors that may influence the accuracy of cervical cancer diagnosis and monitoring.

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Aberrant Methylation of MEG3 Functions as a Potential Plasma-Based Biomarker for Cervical Cancer

Cited by 55 publications

References 22 publications

DNA methylation of imprinted gene control regions in the regression of low‐grade cervical lesions

DNA methylation of imprinted gene control regions in the regression of low‐grade cervical lesions

Reconstruction and analysis of the aberrant lncRNA‐miRNA‐mRNA network based on competitive endogenous RNA in CESC

Diagnostic value of circulating tumor DNA as an effective biomarker in cervical cancer: a meta-analysis

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