Dataset Information

Genome-wide DNA methylation markers associated with metabolic liver cancer

ABSTRACT: Background and Aims: Metabolic liver disease is the fastest rising cause of hepatocellular carcinoma (HCC) worldwide, but the underlying molecular processes that drive HCC development in the setting of metabolic perturbations are unclear. We investigated the role of aberrant DNA methylation in metabolic HCC development in a multicenter international study. Results: We enrolled 272 metabolic HCC patients and 316 control patients with metabolic liver disease from six sites. Fifty-five differentially methylated CpGs were identified; 33 hypermethylated and 22 hypomethylated in cases versus controls. The panel of 55 CpGs discriminated between cases and controls with AUC=0.79 (95%CI=0.71-0.87), sensitivity=0.77 (95%CI=0.66-0.89), and specificity=0.74 (95%CI=0.64-0.85). The 55-CpG classifier panel performed better than a base model that comprised age, sex, race, and diabetes mellitus (AUC=0.65, 95%CI=0.55-0.75, sensitivity=0.62 (95%CI=0.49-0.75) and specificity=0.64 (95%CI=0.52-0.75). A multifactorial model that combined the 55 CpGs with age, sex, race, and diabetes, yielded AUC=0.78 (95%CI=0.70-0.86), sensitivity=0.81 (95%CI=0.71-0.92), and specificity=0.67 (95%CI=0.55-0.78). Conclusions: A panel of 55 blood leukocyte DNA methylation markers differentiates patients with metabolic HCC from control patients with benign metabolic liver disease, with a slightly higher sensitivity when combined with demographic and clinical information.

ORGANISM(S): Homo sapiens

PROVIDER: GSE281691 | GEO | 2025/02/26

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Differentially methylated oral squamous cell carcinoma (OSCC) biomarkers, identified in-vitro and validated in well-characterized surgical specimens, have shown poor clinical correlation in cohorts with different risk profiles. To overcome this lack of relevance we used the HumanMethylation27 BeadChip, publicly available methylation and expression array data, and Quantitative Methylation Specific PCR to uncover differential methylation in OSCC clinical samples with heterogeneous risk profiles. A two stage-design consisting of Discovery and Prevalence screens was used to identify differential promoter methylation and deregulated pathways in patients diagnosed with OSCC and head and neck squamous cell carcinoma. Promoter methylation of KIF1A (k=0.64), HOXA9 (k=0.60), NID2 (k=0.60), and EDNRB (k=0.60) had a moderate to substantial agreement with clinical diagnosis in the Discovery screen. HOXA9 had 68% sensitivity, 100% specificity and a 0.81 AUC. NID2 had 71% sensitivity, 100% specificity and a 0.79 AUC. In the Prevalence screen HOXA9 (k=0.82) and NID2 (k=0.80) had an almost perfect agreement with histologic diagnosis. HOXA9 had 85% sensitivity, 97% specificity and a 0.95 AUC. NID2 had 87% sensitivity, 95% specificity and a 0.91 AUC. A HOXA9 and NID2 gene panel had 94% sensitivity, 97% specificity and a 0.97 AUC. In saliva from OSCC cases and controls HOXA9 had 75% sensitivity, 53% specificity and a 0.75 AUC. NID2 had 87% sensitivity, 21% specificity and a 0.73 AUC. This Phase I Biomarker Development Trial identified a panel of differentially methylated genes in normal and OSCC clinical samples from patients with heterogeneous risk profiles. This panel may be useful for early detection and cancer prevention studies. The 12 samples analyzed comprise equal numbers of three tissue-types: Primary oral squamous cell carcinoma, Oral leukoplakia and Normal oral mucosa. Gender, age and smoking-status were approximately equally represented in these goups. Normal oral mucosa served as a control.

Dataset Information

Genome-wide DNA methylation markers associated with metabolic liver cancer

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets