UNASSIGNED: The objective of this study was to verify the clinical predictive performance of methylated cysteine dioxygenase type 1 (CDO1m) and CUGBP Elav-like family member 4 (CELF4m) in endometrial cancer (EC) women with postmenopausal bleeding (PMB).
UNASSIGNED: A single-center, prospective, and case-control study was conducted in the Gansu Provincial Maternity and Child-care Hospital with 138 female postmenopausal patients enrolled in 2022. All patients underwent body mass index (BMI) detection, transvaginal ultrasonography (TVUS) detection, carbohydrate antigen 125 detection, and the cervical exfoliated cell CDO1/CELF4 gene methylation detection to analyze the sensitivity, specificity, and accuracy of different screening tests statistically with the biopsy and/or dilation and curettage (D&C) pathological diagnosis under hysteroscopy as the gold standard.
UNASSIGNED: There was no significant difference in age between the EC group and the non-EC group, P = 0.492. Using quantitative polymerase chain reaction (qPCR) technology, we validated the CDO1 and CELF4 methylation detection with 87.5% sensitivity and 95.9% specificity as a useful strategy for the triage of women with PMB for the detection of EC. In addition, 100% of type II EC (n = 6) were positively detected by the CDO1 or CELF4 methylation test.
UNASSIGNED: The CDO1 and CELF4 methylation test with high specificity as an auxiliary diagnostic tool or alternative method provides physicians with a reference to distinguish between benign and malignant tumors in women with postmenopausal bleeding, to justify the necessity of using invasive methods to confirm diagnosis.

An observational cohort study of patients diagnosed with endometrial cancer (EC) stage IA G1, or atypical endometrial hyperplasia (AEH), undergoing organ-preserving treatment, was conducted.
OBJECTIVE: To determine CDO1, PITX2, and CDH13 gene methylation levels in early endometrial cancer and atypical hyperplasia specimens obtained before organ-preserving treatment in the patients with adequate response and with insufficient response to hormonal treatment.
METHODS: A total of 41 endometrial specimens obtained during diagnostic uterine curettage in women with EC (n = 28) and AEH (n = 13), willing to preserve reproductive function, were studied; 18 specimens of uterine cancer IA stage G1 from peri- and early postmenopausal women (comparison group) were included in the study. The control group included 18 endometrial specimens from healthy women obtained by diagnostic curettage for missed abortion and/or intrauterine adhesions. Methylation levels were analyzed using the modified MS-HRM method.
RESULTS: All 13 women with AEH had a complete response (CR) to medical treatment. In the group undergoing organ-preserving treatment for uterine cancer IA stage G1 (n = 28), 14 patients had a complete response (EC CR group) and 14 did not (EC non-CR group). It was found that all groups had statistically significant differences in CDO1 gene methylation levels compared to the control group (p < 0.001) except for the EC CR group (p = 0.21). The p-value for the difference between EC CR and EC non-CR groups was <0.001. The differences in PITX2 gene methylation levels between the control and study groups were also significantly different (p < 0.001), except for the AEH group (p = 0.21). For the difference between EC CR and EC non-CR groups, the p-value was 0.43. For CDH13 gene methylation levels, statistically significant differences were found between the control and EC non-CR groups (p < 0.001), and the control and EC comparison groups (p = 0.005). When comparing the EC CR group with EC non-CR group, the p-value for this gene was <0.001. The simultaneous assessment of CDO1 and CDH13 genes methylation allowed for an accurate distinction between EC CR and EC non-CR groups (AUC = 0.96).
CONCLUSIONS: The assessment of CDO1 and CDH13 gene methylation in endometrial specimens from patients with endometrial cancer (IA stage G1), scheduled for medical treatment, can predict the treatment outcome.

Cysteine dioxygenase type 1 (Cdo1) is a tumor suppressor gene. It regulates the metabolism of cysteine, thereby influencing the cellular antioxidative capacity. This function puts Cdo1 in a prominent position to promote ferroptosis and apoptosis. Cdo1 promotes ferroptosis mainly by decreasing the amounts of antioxidants, leading to autoperoxidation of the cell membrane through Fenton reaction. Cdo1 promotes apoptosis mainly through the product of cysteine metabolism, taurine, and low level of antioxidants. Many cancers exhibit altered function of Cdo1, underscoring its crucial role in cancer cell survival. Genetic and epigenetic alterations have been found, with methylation of Cdo1 promoter as the most common mutation. The fact that no cancer was found to be caused by altered Cdo1 function alone indicates that the tumor suppressor role of Cdo1 is mild. By compiling the current knowledge about apoptosis, ferroptosis, and the role of Cdo1, this review suggests possibilities for how the mild anticancer role of Cdo1 could be harnessed in new cancer therapies. Here, developing drugs targeting Cdo1 is considered meaningful in neoadjuvant therapies, for example, helping against the development of anti-cancer drug resistance in tumor cells.

Liver is a major organ that metabolizes sulfur amino acids cysteine, which is the substrate for the synthesis of many essential cellular molecules including GSH, taurine, and coenzyme A. Bile acid-activated farnesoid x receptor (FXR) inhibits cysteine dioxygenase type 1 (CDO1), which mediates hepatic cysteine catabolism and taurine synthesis. To define the impact of bile acid inhibition of CDO1 on hepatic sulfur amino acid metabolism and antioxidant capacity, we developed hepatocyte-specific CDO1 knockout mice (Hep-CDO1 KO) and hepatocyte specific CDO1 transgenic mice (Hep-CDO1 Tg). Liver metabolomics revealed that genetic deletion of hepatic CDO1 reduced de novo taurine synthesis but had no impact on hepatic taurine abundance or bile acid conjugation. Consistent with reduced cysteine catabolism, Hep-CDO1 KO mice showed increased hepatic cysteine abundance but unaltered methionine cycle intermediates and coenzyme A synthesis. Upon acetaminophen overdose, Hep-CDO1 KO mice showed increased GSH synthesis capacity and alleviated liver injury. In contrast, hepatic CDO1 overexpression in Hep-CDO1 Tg mice stimulated hepatic cysteine to taurine conversion, resulting in reduced hepatic cysteine abundance. However, Hep-CDO1 Tg mice and WT showed similar susceptibility to acetaminophen-induced liver injury. Hep-CDO1 Tg mice showed similar hepatic taurine and coenzyme A compared to WT mice. In summary, these findings suggest that bile acid and FXR signaling inhibition of CDO1-mediated hepatic cysteine catabolism preferentially modulates hepatic GSH synthesis capacity and antioxidant defense, but has minimal effect on hepatic taurine and coenzyme A abundance. Repression of hepatic CDO1 may contribute to the hepatoprotective effects of FXR activation under certain pathologic conditions.

DNMT3L is a crucial DNA methylation regulatory factor, yet its function and mechanism in hepatocellular carcinoma (HCC) remain poorly understood. Bioinformatics-based big data analysis has increasingly gained significance in cancer research. Therefore, this study aims to elucidate the role of DNMT3L in HCC by integrating big data analysis with experimental validation.
Dozens of HCC datasets were collected to analyze the expression of DNMT3L and its relationship with prognostic indicators, and were used for molecular regulatory relationship evaluation. The effects of DNMT3L on the malignant phenotypes of hepatoma cells were confirmed in vitro and in vivo. The regulatory mechanisms of DNMT3L were explored through MSP, western blot, and dual-luciferase assays.
DNMT3L was found to be downregulated in HCC tissues and associated with better prognosis. Overexpression of DNMT3L inhibits cell proliferation and metastasis. Additionally, CDO1 was identified as a target gene of DNMT3L and also exhibits anti-cancer effects. DNMT3L upregulates CDO1 expression by competitively inhibiting DNMT3A-mediated methylation of CDO1 promoter.
Our study revealed the role and epi-transcriptomic regulatory mechanism of DNMT3L in HCC, and underscored the essential role and applicability of big data analysis in elucidating complex biological processes.

Cysteine 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.
We 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.
CDO1 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.
CDO1 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.

Extensive data research is helpful to find sensitive biomarkers for prognostic prediction of metastatic breast cancer. Through analyzing multiple GEO datasets, literature retrieval, and verified in GEPIA datasets, we identify BIRC5 (Baculoviral IAP repeat containing 5) and CDO1 (Cysteine dioxygenase type 1) as DEGs (differentially expressed genes) between breast tumor and normal tissue and DEGs between metastatic breast cancer and breast cancer in situ. Then, we performed a series of in silico studies on BIRC5 and CDO1 using online tools including the UALCAN, TIMER, TCGA-BRCA, LinkedOmics Kaplan-Meier Plotter, and an R script for analysis. To verify the association of 2 genes expression and patients\' clinical data, we detected BIRC5 and CDO1 mRNA in the tissue of 48 breast cancer patients. The results showed the tumor with BIRC5high CDO1low expression generally indicated patients\' shorter overall (OS) and relapse-free survival (RFS). Specifically, BIRC5 and CDO1 levels significantly affect OS or RFS in patients with Lymph node metastasis and molecular subtypes of TNBC (triple-negative breast cancer) and Luminal A. A BIRC5high tumor displayed a purer tumor purity and expressed more KIR receptors on NK cells while activating more FOXP3+CD25+ Treg cells. The CDO1low tumors infiltrated with more immunocytes leading to less tumor purity. In our verified experiment, BIRC5 mRNA level in patients with stage III and over was significantly higher than in patients with stage 0 to II, but there were no significant differences among molecular subtyping groups; TNBC tissue expressed lower CDO1 mRNA level than HER2+ and Luminal type cancer tissue. In conclusion, a BIRC5high CDO1low expression type in breast cancer tissue indicates a poorer prognosis of patients. The potential mechanism might be increased BIRC5 expression in cancer tissue is likely to accompany NK cells inhibition, activating more Treg cells, and lacking effective CD8+ T cells proliferation. Meanwhile, CDO1 level is positively related to more immunocytes infiltration.

The long reads of Nanopore sequencing permit accurate transcript assembly and ease in discovering novel transcripts with potentially important functions in cancers. The wide adoption of Nanopore sequencing for transcript quantification, however, is largely limited by high costs. To address this issue, we developed a bioinformatics software, NovelQuant, that can specifically quantify long-read-assembled novel transcripts with short-read sequencing data. Nanopore Direct RNA Sequencing was carried out on three hepatocellular carcinoma (HCC) patients\' tumor, matched portal vein tumor thrombus, and peritumor to reconstruct the HCC transcriptome. Then, based on the reconstructed transcriptome, NovelQuant was applied on Illumina RNA sequencing data of 59 HCC patients\' tumor and paired peritumor to quantify novel transcripts. Our further analysis revealed 361 novel transcripts dysregulated in HCC and that 101 of them were significantly associated with prognosis. There were 19 novel prognostic transcripts predicted to be long noncoding RNAs (lncRNAs), and some of them had regulatory targets that were reported to be associated with HCC. Additionally, 42 novel prognostic transcripts were predicted to be protein-coding mRNAs, and many of them could be involved in xenobiotic metabolism. Moreover, the tumor-suppressive roles of two representative novel prognostic transcripts, CDO1-novel (lncRNA) and CYP2A6-novel (protein-coding mRNA), were further functionally validated during HCC progression. Overall, the current study shows a possibility of combining long- and short-read sequencing to explore functionally important novel transcripts in HCC with accuracy and cost-efficiency, which expands the pool of molecular biomarkers that could enhance our understanding of the molecular mechanisms of HCC.

CDO1 is a presumed tumor suppressor gene in human cancers, the expression of which is silenced by promoter DNA methylation. Moreover, CDO1 harbors functionally oncogenic aspects through modification of mitochondrial membrane potential. We recently proposed that this oncogenic feature allows for the prediction of the efficacy of postoperative chemotherapy in colon cancer. The present study aims to elucidate the efficacy of prediction of success of postoperative chemotherapy in advanced gastric cancer to improve the treatment strategy of patients.
Forced expression of CDO1 in gastric cancer cell lines was assessed using the JC-1 assay. Promoter DNA methylation was investigated in quantitative TaqMan methylation-specific polymerase chain reaction in 321 pathological stage II/III advanced gastric cancer cases treated by curative gastrectomy with or without postoperative chemotherapy.
(1) Forced expression of CDO1 led to increased mitochondrial membrane potential, accompanied by augmented survival in gastric cancer cells under anaerobic conditions. These results suggest that CDO1-expressing cancer cells survive more easily in anaerobic lesions which are inaccessible to anticancer drugs. (2) Intriguingly, in cases with the highest CDO1 methylation (ranging from 15% to 40%), patients with postoperative chemotherapy showed significantly better survival than those with no postoperative chemotherapy. (3) A robust prognostic difference was observed that was explained by differential recurrences of distant metastasis (P = 0.0031), followed by lymph node (P = 0.0142) and peritoneal dissemination (P = 0.0472).
The oncogenic aspects of CDO1 can be of use to determine patients with gastric cancer who will likely respond to treatment of invisible systemic dissemination by postoperative adjuvant chemotherapy.

BACKGROUND: The incidence and mortality of lung cancer often rank first in all malignant tumors. DNA methylation, as one of epigenetics, often participates in the development and progression of tumors. CDO1 as a tumor suppressor gene always undergoes methylation changes early in tumor development. Therefore, this study aims to discuss the value of CDO1 methylation in the early diagnosis of lung cancer.
METHODS: Peripheral blood samples were collected from tumor patients and healthy people. Detection of the methylation level of CDO1 in plasma by sulfite modification and quantitative real-time PCR.
RESULTS: The level of gene methylation in peripheral blood of lung cancer patients was significantly higher than that of benign lung disease patients and healthy people. The methylation level of CDO1 was significantly different in the stratified comparison of gender, lymph node metastasis and tumor-node-metastasis (TNM) stage (P<0.05). The sensitivity and specificity of CDO1 were 52.2% and 78.6%, respectively. The overall accuracy of the diagnosis was significantly higher than that of the clinical tumor markers, and the sensitivity of CDO1 to stage I and II patients was the highest (40.8%, 47.1%). In addition, CDO1 could effectively increase the sensitivity of diagnosis in multiple joint examinations.
CONCLUSIONS: Detecting the methylation level of CDO1 has a potentially huge advantage for the early diagnosis of lung cancer.
【中文题目：血浆中CDO1甲基化在肺癌早期诊断中的作用研究】 【中文摘要：背景与目的 肺癌的发生率和死亡率常居所有恶性肿瘤的首位，DNA甲基化作为表观遗传学之一参与肿瘤的发生发展过程，CDO1作为抑癌基因常在肿瘤发生早期便会发生甲基化改变，因此本研究旨在探讨CDO1甲基化在肺癌早期诊断中的价值。方法 收集肿瘤患者和健康人群的外周血液样本，游离DNA通过亚硫酸盐修饰并结合实时荧光定量PCR检测CDO1在外周血中的甲基化水平。结果 肺癌患者的外周血的基因甲基化水平明显高于肺部良性疾病患者及健康人群。肺癌患者CDO1的甲基化水平在性别、淋巴结转移和肿瘤原发灶-淋巴结-转移（tumor-node-metastasis, TNM）分期的分层比较中存在显著性差异（P<0.05）。CDO1对肺癌诊断的灵敏度和特异性分别为52.2%和78.6%。其诊断的整体准确度明显高于应用于临床的肿瘤标志物而且对I期、II期患者的诊断灵敏度表现最好（40.8%, 47.1%）。此外，CDO1可有效增加多项联检中诊断的灵敏性。结论 检测CDO1的甲基化水平对肺癌的早期诊断具有潜在的巨大优势。】 【中文关键词：半胱氨酸双加氧酶1；甲基化；DNA；肺肿瘤；血浆】.