Integrated Epigenomics Analysis Reveals a DNA Methylation Panel for Endometrial Cancer Detection Using Cervical Scrapings

Huang, Rui; Su, Po Hsuan; Liao, Yu Ping; Wu, Ting-Jung; Hsu, Ya Ting; Lin, Wei Yu; Wang, Hui Chen; Weng, Yu Chun; Ou, Yu‐Che; Huang, Tim H.M.; Lai, Hung Cheng

doi:10.1158/1078-0432.ccr-16-0863

Cited by 69 publications

(72 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…for instance, through testing of endoscopic retrograde cholangiopancreatography (ERCP) brushing solution in biliary tract cancer 49 and cervical scrapings in endometrial cancer. 42 .0001). B, In gallbladder carcinogenesis, the CDO1 methylation level increased significantly as the disease progressed from stage I to stage II the peritoneum, which was all positive for CY1 cases ( Figure 5A), and can predict peritoneal recurrence accurately.…”

Section: An Cer De Tec Ti On Marker Of CD O1 G Ene Me Thyl Ati Onmentioning

confidence: 96%

“…Since 2010, the frequent hypermethylation of the CDO1 gene has been reported in primary breast, lung, biliary tract, esophageal squamous cell carcinoma (SCC) and adenocarcinoma, gastric, colorectal, bladder, penile (SCC), kidney, prostate, endometrial, pancreatic and gallbladder cancer . The frequencies of the aberrations in CDO1 methylation in these cancers are high (Figure A).…”

Section: The Best Performance As An Epigenetic Cancer Biomarker: Cdo1mentioning

confidence: 99%

“…CDO1 hypermethylation could be useful for assisting preoperative disease diagnosis in critical body fluids other than plasma: for instance, through testing of endoscopic retrograde cholangio‐pancreatography (ERCP) brushing solution in biliary tract cancer and cervical scrapings in endometrial cancer . These body fluids are important for diagnosis, because inaccurate diagnosis would lead to unnecessary invasive surgery (false positive) or to missing the true disease (false negative).…”

Section: Cancer Detection Marker Of Cdo1 Gene Methylation In Human Bomentioning

confidence: 99%

“…Cytology testing of ERCP brushing solution can be used to diagnose biliary tract cancer in approximately 60% of cases, while the CDO1 methylation cytology test showed a high AUC of .93 in predicting biliary tract cancer . Cervical scrapings were reported as a potential source of material for molecular testing in endometrial cancer, and CDO1 hypermethylation amazingly showed an 82% sensitivity with 94% specificity for detecting endometrial cancer in cervical scrapings …”

Section: Cancer Detection Marker Of Cdo1 Gene Methylation In Human Bomentioning

confidence: 99%

“…The HRMG profile of endometrial cancer is different from that of cervical SCC cancer; however, the combination of HRMG showed more successful performance in the former than in the latter. Specifically, the BHLHE22 / CDO1 / CELF4 combinations of methylation markers showed 92% sensitivity with 95% specificity in scrapings tests . Given that there have been no descriptions of methylation frequencies of primary tumors for assessing whether CDO1 is an HRMG in this disease, that gene was not included as an HRMG for endometrial cancer in Table .…”

Section: Clinical Decision By Combination Of Highly Relevant Methylatmentioning

confidence: 99%

See 4 more Smart Citations

Epigenetic biomarkers of promoter DNA methylation in the new era of cancer treatment

et al. 2018

View full text Add to dashboard Cite

Promoter DNA methylation, which occurs on cytosine nucleotides across CpG islands, results in gene silencing and represents a major epigenetic alteration in human cancer. Methylation‐specific PCR can amplify these modifications as markers in cancer cells. In the present work, we rigorously review the published literatures describing DNA methylation in the promoters of critical tumor suppressor genes; detection of promoter DNA methylation in various body fluids permits early detection of cancer cells during perioperative courses of clinical treatment. The latest whole‐genome comprehensive explorations identified excellent epigenetic biomarkers that could be detected at high frequency with high specificity; these biomarkers, which are designated highly relevant methylation genes (HRMG), permit the discrimination of tumor tissues from the corresponding normal tissues; these markers are also associated with unique cancer phenotypes, including dismal prognosis. In humans, HRMG include the CDO1,GSHR,RASSF1 and SFRP1 genes, with these markers permitting discrimination depending on the organs tested. The combination of several HRMG increased the early detection of cancer and exhibited reliable surveillance potential in human body fluids. Cancer clinics using such epigenetic biomarkers are entering a new era of enhanced decision‐making with the potential for improved cancer prognosis.

show abstract

Section: An Cer De Tec Ti On Marker Of CD O1 G Ene Me Thyl Ati Onmentioning

confidence: 96%

Section: The Best Performance As An Epigenetic Cancer Biomarker: Cdo1mentioning

confidence: 99%

Section: Cancer Detection Marker Of Cdo1 Gene Methylation In Human Bomentioning

confidence: 99%

Section: Cancer Detection Marker Of Cdo1 Gene Methylation In Human Bomentioning

confidence: 99%

Section: Clinical Decision By Combination Of Highly Relevant Methylatmentioning

confidence: 99%

See 3 more Smart Citations

Epigenetic biomarkers of promoter DNA methylation in the new era of cancer treatment

et al. 2018

View full text Add to dashboard Cite

show abstract

Identification and validation of novel DNA methylation markers for early diagnosis of lung adenocarcinoma

Zhang

Zhou

et al. 2020

Molecular Oncology

View full text Add to dashboard Cite

Lung cancer has the highest mortality of all cancers worldwide. Epigenetic alterations have emerged as potential biomarkers for early diagnosis of various cancer tissue types. To identify methylation markers for early diagnosis of lung adenocarcinoma, we aimed to integrate genome-wide DNA methylation and gene expression data from The Cancer Genome Atlas. To this end, we first examined the global DNA methylation pattern of lung adenocarcinoma and investigated the relationship between DNA methylation subtypes and clinical features. We then extracted differentially methylated and expressed genes, and adopted feature selection techniques to determine the final methylation markers. The performance of the markers in predicting lung adenocarcinoma was evaluated on three independent datasets from Gene Expression Omnibus. Protein levels of marker genes were validated by immunohistochemistry, and their biological function was further verified in vivo. We identified three novel methylation markers in lung adenocarcinoma including cg08032924, cg14823851, and cg19161124, mapping to CMTM2, TBX4, and DPP6, respectively. Validating these results on three independent datasets indicated that the three markers can achieve extremely high sensitivity and specificity in distinguishing lung adenocarcinoma from normal samples. Immunohistochemistry quantification results confirmed that markers are weakly expressed in human lung adenocarcinoma, and CMTM2 decreased tumor growth of mouse Lewis lung carcinoma in vivo. Overall, our study identified three novel methylation markers in lung adenocarcinoma which may contribute toward an improved diagnosis potentially leading to a better outcome for patients with lung adenocarcinoma.

show abstract

Identification of aberrantly methylated differentially expressed genes and associated pathways in endometrial cancer using integrated bioinformatic analysis

Liu

Wan

et al. 2020

Cancer Medicine

View full text Add to dashboard Cite

Endometrial cancer (EC) is a fatal female reproductive tumor. Bioinformatic tools are increasingly developed to screen out molecular targets related to EC. In this study, GSE17025 and GSE40032 were obtained from Gene Expression Omnibus (GEO). “limma” package and Venn diagram tool were used to identify hub genes. FunRich was used for functional analysis. Retrieval of Interacting Genes Database (STRING) was used to analyze protein‐protein interaction (PPI) complex. Cancer Genome Atlas (TCGA), GEPIA, immunohistochemistry staining, and ROC curve analysis were carried out for validation. Univariate and multivariate regression analyses were performed to predict the risk score. Compound muscle action potential (CMap) was used to find potential drugs. GSEA was also done. We retrieved seven oncogenes which were upregulated and hypomethylated and 12 tumor suppressor genes (TSGs) which were downregulated and hypermethylated. The upregulated and hypomethylated genes were strikingly enriched in term “immune response” while the downregulated and hypermethylated genes were mainly focused on term “aromatic compound catabolic process.” TCGA and GEPIA were used to screen out EDNRB, CDO1, NDN, PLCD1, ROR2, ESPL1, PRAME, and PTTG1. Among them, ESPL1 and ROR2 were identified by Cox regression analysis and were used to construct prognostic risk model. The result showed that ESPL1 was a negative independent prognostic factor. Cmap identified aminoglutethimide, luteolin, sulfadimethoxine, and maprotiline had correlation with EC. GSEA results showed that “hedgehog signaling pathway” was enriched. This research inferred potential aberrantly methylated DEGs and dysregulated pathways may participate in EC development and firstly reported eight hub genes, including EDNRB, CDO1, NDN, PLCD1, ROR2, ESPL1, PRAME, and PTTG1 that could be used to predict EC prognosis. Aminoglutethimide and luteolin may be used to fight against EC.

show abstract

Integrated Epigenomics Analysis Reveals a DNA Methylation Panel for Endometrial Cancer Detection Using Cervical Scrapings

Abstract: This study demonstrates the potential use of methylated BHLHE22/CDO1/CELF4 panel for endometrial cancer screening of cervical scrapings. Clin Cancer Res; 23(1); 263-72. ©2016 AACR.

Cited by 69 publications

References 51 publications

Epigenetic biomarkers of promoter DNA methylation in the new era of cancer treatment

Epigenetic biomarkers of promoter DNA methylation in the new era of cancer treatment

Identification and validation of novel DNA methylation markers for early diagnosis of lung adenocarcinoma

Identification of aberrantly methylated differentially expressed genes and associated pathways in endometrial cancer using integrated bioinformatic analysis

Contact Info

Product

Resources

About