Prognostic significance of promoter DNA hypermethylation of the cysteine dioxygenase 1 (CDO1) gene in primary gallbladder cancer and gallbladder disease

Igarashi, Kento; Yamashita, Keishi; Katoh, Hiroshi; Kojima, Kiyoshi; Ooizumi, Yosuke; Nishizawa, Nobuyuki; Nishiyama, Ryo; Kawamata, Hiroshi; Kubo, Takashi; Kumamoto, Yusuke; Watanabe, Masahiko

doi:10.1371/journal.pone.0188178

Cited by 18 publications

(33 citation statements)

References 27 publications

(36 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Specifically in esophageal cancer, CDO1 methylation was significantly higher in advanced SCC tumors with cStage II/III than in the superficial tumors with cStage I, and was significantly higher in larger‐sized adenocarcinomas than in smaller‐sized adenocarcinomas . Aberrant methylation of the CDO1 gene accumulated as the tumor progressed, as demonstrated in colorectal and gallbladder tumorigenesis (Figure A,B). These findings indicate that promoter DNA methylation of the CDO1 gene commonly accumulates with progression in human cancers.…”

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

confidence: 89%

“…Cases with CDO1 hypermethylation also showed poorer prognosis than those with hypomethylation in primary breast, prostate, colorectal, gallbladder and esophageal cancers . Interestingly, in primary breast cancer, CDO1 hypermethylation did not correlate significantly with markers of tumor progression such as TNM factors, while CDO1 hypermethylation was the strongest independent prognostic factor .…”

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

confidence: 91%

“…Since 2010, the frequent hypermethylation of the CDO1 gene has been reported in primary breast, 33,34 lung, 19 biliary tract, 35 esophageal squamous cell carcinoma (SCC) 36 and adenocarcinoma, 37 gastric, 19 colorectal, 19,38 bladder, 19 penile (SCC), 39 kidney, 40 prostate, 41 endometrial, 42 pancreatic 43 and gallbladder cancer. 44 The frequencies of the aberrations in CDO1 methylation in these cancers are high ( Figure 3A). Intriguingly, however, there are several unique cancers in which the CDO1 gene did not show an HRMG phenotype: for instance, renal cell clear carcinoma.…”

Section: The B E S T Performan Ce a S An Epi G Ene Ti C C An Cer B mentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2018

Self Cite

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: The Best Performance As An Epigenetic Cancer Biomarker: Cdo1mentioning

confidence: 89%

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

confidence: 91%

Section: The B E S T Performan Ce a S An Epi G Ene Ti C C An Cer B mentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…Total RNA from cell lines was extracted using RNeasy Mini Kit (Qiagen), and was reverse‐transcribed with a Super Script III reverse transcriptase kit (Invitrogen). Primers sequences for CDO1 and β ‐actin were described previously . Reverse transcription‐PCR was undertaken by 30 cycles of 95°C for 1 minute, 58°C for 1 minute, and 72°C for 1 minute.…”

Section: Methodsmentioning

confidence: 99%

“…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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Targeted demethylation of the CDO1 promoter based on CRISPR system inhibits the malignant potential of breast cancer cells

Yang,

Sun,

Liu

et al. 2023

Clinical & Translational Med

View full text Add to dashboard Cite

BackgroundCysteine dioxygenase 1 (CDO1) is frequently methylated, and its expression is decreased in many human cancers including breast cancer (BC). However, the functional and mechanistic aspects of CDO1 inactivation in BC are poorly understood, and the diagnostic significance of serum CDO1 methylation remains unclear.MethodsWe performed bioinformatics analysis of publicly available databases and employed MassARRAY EpiTYPER methylation sequencing technology to identify differentially methylated sites in the CDO1 promoter of BC tissues compared to normal adjacent tissues (NATs). Subsequently, we developed a MethyLight assay using specific primers and probes for these CpG sites to detect the percentage of methylated reference (PMR) of the CDO1 promoter. Furthermore, both LentiCRISPR/dCas9‐Tet1CD‐based CDO1‐targeted demethylation system and CDO1 overexpression strategy were utilized to detect the function and underlying mechanism of CDO1 in BC. Finally, the early diagnostic value of CDO1 as a methylation biomarker in BC serum was evaluated.ResultsCDO1 promoter was hypermethylated in BC tissues, which was related to poor prognosis (p < .05). The CRISPR/dCas9‐based targeted demethylation system significantly reduced the PMR of CDO1 promotor and increased CDO1 expression in BC cells. Consequently, this leads to suppression of cell proliferation, migration and invasion. Additionally, we found that CDO1 exerted a tumour suppressor effect by inhibiting the cell cycle, promoting cell apoptosis and ferroptosis. Furthermore, we employed the MethyLight to detect CDO1 PMR in BC serum, and we discovered that serum CDO1 methylation was an effective non‐invasive biomarker for early diagnosis of BC.ConclusionsCDO1 is hypermethylated and acts as a tumour suppressor gene in BC. Epigenetic editing of abnormal CDO1 methylation could have a crucial role in the clinical treatment and prognosis of BC. Additionally, serum CDO1 methylation holds promise as a valuable biomarker for the early diagnosis and management of BC.

show abstract

Prognostic significance of promoter DNA hypermethylation of the cysteine dioxygenase 1 (CDO1) gene in primary gallbladder cancer and gallbladder disease

Cited by 18 publications

References 27 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

Targeted demethylation of the CDO1 promoter based on CRISPR system inhibits the malignant potential of breast cancer cells

Contact Info

Product

Resources

About