DNA diagnosis of peritoneal fluid cytology test by CDO1 promoter DNA hypermethylation in gastric cancer

Ushiku, Hideki; Yamashita, Keishi; Ema, Akira; Minatani, Naoko; Kikuchi, Masatoshi; Kojo, Ken; Yokoi, Keigo; Tanaka, Toshimichi; Nishizawa, Nobuyuki; Ishii, Satoru; Hosoda, Kei; Moriya, Hiromitsu; Mieno, Hiroaki; Katada, Natsuya; Kikuchi, Shiro; Katoh, Hiroshi; Watanabe, Masahiko

doi:10.1007/s10120-017-0697-6

Cited by 31 publications

(29 citation statements)

References 28 publications

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“…However, the conventional cytology test does not achieve sufficient sensitivity because peritoneal recurrences have been recognized in cytology‐negative (CY0) cases. DNA cytology testing using CDO1 methylation showed 2‐fold higher detection rates of the minimal residual disease than did conventional CY tests in the peritoneum, which was all positive for CY1 cases (Figure A), and can predict peritoneal recurrence accurately . DNA CY1 diagnosis in the peritoneum would be beneficial for planning future multimodal therapy in gastric cancer after curative surgery.…”

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

confidence: 99%

“…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. 50 DNA CY1 diagnosis in the peritoneum would be beneficial for planning future multimodal therapy in gastric cancer after curative surgery.…”

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

confidence: 99%

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

et al. 2018

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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.

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

confidence: 99%

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

confidence: 99%

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

et al. 2018

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“…CDO1 plays a role as a tumor suppressor gene. As it is a methylation‐specific gene in human cancer, CDO1 methylation has been recently reported in a variety of cancers, such as esophageal, lung, gastric, breast, biliary tract, colorectal, kidney, prostate, bladder, penile, and uterine cancers . However, there has been no report on the involvement of CDO1 in PDAC.…”

Section: Introductionmentioning

confidence: 99%

Diagnostic potential of hypermethylation of the cysteine dioxygenase 1 gene (CDO1) promoter DNA in pancreatic cancer

et al. 2019

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DNA markers for pancreatic ductal adenocarcinoma (PDAC) are urgently needed for detection of minimally invasive disease. The epigenetic relevance of the cysteine dioxygenase 1 gene (CDO1) has been never investigated in PDAC. Three studies, including cellular experiments, tissue validation, and pilot testing for pancreatic cytology, were carried out. Promoter DNA methylation value (MV) of CDO1 was quantified by quantitative methylation‐specific PCR. CDO1 expression was consistent with its promoter DNA methylation in 7 PDAC cell lines. In 160 retrospectively collected primary PDAC tumor tissues, MV was significantly higher compared to the corresponding noncancerous pancreas (area under the receiver operating characteristic curve [AUC] = 0.97, P < .0001), and CDO1 hypermethylation was highly specific to PDAC tumor tissues. CDO1 hypermethylation group (MV over 19) was significantly associated with diverse prognostic factors in PDAC. Surprisingly, it was significantly higher in prospectively collected PDAC cytology samples (n = 37), including both pancreatic juice (n = 12) and endoscopic ultrasound‐fine needle aspiration (EUS‐FNA) cytology (n = 25) compared to pancreatic benign diseases (AUC = 0.96, P < .0001). Detection of PDAC was confirmed by DNA testing in 35 of 37 patients (95% sensitivity); thus, it was more sensitive than cytology (33%) or EUS‐FNA cytology (88%). Promoter DNA methylation of CDO1 is extremely specific for PDAC tumors, and accumulates with PDAC tumor progression. It could be a definitive diagnostic marker of PDAC in pancreatic juice or EUS‐FNA cytology.

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“…Brait et al reported that CDO1 serves as a tumor suppressor and is deactivated by promoter methylation in several tumors [31]. Jeschke et al cancer [34], breast cancer [35], hepatocellular carcinoma [36], and prostate cancer [37]. Sirnes et al reported that GJC1 promoter methylation played a crucial role in colorectal cancer [38] and follicular lymphoma [39].…”

Section: Discussionmentioning

confidence: 99%

Combined Analysis of the Aberrant Epigenetic Alteration of Pancreatic Ductal Adenocarcinoma

Huang

et al. 2019

BioMed Research International

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Background. Pancreatic ductal adenocarcinoma (PDAC) remains one of the most fatal malignancies due to its high morbidity and mortality. DNA methylation exerts a vital part in the development of PDAC. However, a mechanistic role of mutual interactions between DNA methylation and mRNA as epigenetic regulators on transcriptomic alterations and its correlation with clinical outcomes such as survival have remained largely uncovered in cancer. Therefore, elucidation of aberrant epigenetic alteration in the development of PDAC is an urgent problem to be solved. In this work, we conduct an integrative epigenetic analysis of PDAC to identify aberrant DNA methylation-driven cancer genes during the occurrence of cancer. Methods. DNA methylation matrix and mRNA profile were obtained from the TCGA database. The integration of methylation and gene expression datasets was analyzed using an R package MethylMix. The genes with hypomethylation/hypermethylation were further validated in the Kaplan–Meier analysis. The correlation analysis of gene expression and aberrant DNA methylation was also conducted. We performed a pathway analysis on aberrant DNG methylation genes identified by MethylMix criteria using ConsensusPathDB. Results. 188 patients with both methylation data and mRNA data were considered eligible. A mixture model was constructed, and differential methylation genes in normal and tumor groups using the Wilcoxon rank test was performed. With the inclusion criteria, 95 differential methylation genes were detected. Among these genes, 74 hypermethylation and 21 hypomethylation genes were found. The pathway analysis revealed an increase in hypermethylation of genes involved in ATP-sensitive potassium channels, Robo4, and VEGF signaling pathways crosstalk, and generic transcription pathway. Conclusion. Integrated analysis of the aberrant epigenetic alteration in pancreatic ductal adenocarcinoma indicated that differentially methylated genes could play a vital role in the occurrence of PDAC by bioinformatics analysis. The present work can help clinicians to elaborate on the function of differentially methylated expressed genes and pathways in PDAC. CDO1, GJD2, ID4, NOL4, PAX6, TRIM58, and ZNF382 might act as aberrantly DNA-methylated biomarkers for early screening and therapy of PDAC in the future.

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DNA diagnosis of peritoneal fluid cytology test by CDO1 promoter DNA hypermethylation in gastric cancer

Abstract: DNA CY1 detected by Q-MSP for CDO1 gene promoter DNA methylation has a great potential to detect minimal residual disease of the peritoneum in GC clinics as a novel DNA marker.

Cited by 31 publications

References 28 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

Diagnostic potential of hypermethylation of the cysteine dioxygenase 1 gene (CDO1) promoter DNA in pancreatic cancer

Combined Analysis of the Aberrant Epigenetic Alteration of Pancreatic Ductal Adenocarcinoma

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