Plasma DNA methylation marker and hepatocellular carcinoma risk prediction model for the general population
| Autor: | Qiao Wang, Regina M. Santella, Hwai I. Yang, Hui-Chen Wu, Chien-Jen Chen |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Adult
Male 0301 basic medicine Oncology Cancer Research medicine.medical_specialty Carcinoma Hepatocellular Population Kruppel-Like Transcription Factors Biology Bioinformatics 03 medical and health sciences 0302 clinical medicine Risk Factors Internal medicine Biomarkers Tumor medicine Carcinoma Cyclin-Dependent Kinase Inhibitor p18 Humans education neoplasms Cyclin-Dependent Kinase Inhibitor p16 Cancer Biomarkers and Molecular Epidemiology Aged education.field_of_study Tumor Suppressor Proteins Liver Neoplasms Area under the curve Case-control study Membrane Proteins General Medicine Methylation DNA Methylation Middle Aged medicine.disease digestive system diseases 030104 developmental biology Area Under Curve Case-Control Studies 030220 oncology & carcinogenesis Hepatocellular carcinoma DNA methylation Female Oxidoreductases T-Box Domain Proteins Risk assessment |
| Zdroj: | Carcinogenesis. 38:1021-1028 |
| ISSN: | 1460-2180 0143-3334 |
| Popis: | Metastases in the later stages of hepatocellular carcinoma (HCC) cause the majority of deaths associated with the disease, making early detection crucial to patient survival. Risk models assessing HCC risk in the general population can be used for risk stratification for further HCC surveillance, however, none have been validated externally. Methylation of circulating DNA shows potential for non-invasive diagnosis of HCC. We conducted a prospective case-control study nested within a community-based cohort. We measured methylation levels in six genes (CDKN2A, RASSF1A, STEAP4, TBX2, VIM and ZNF154) which were identified in our previous work, using pre-diagnostic plasma DNA from 237 HCC cases and 257 matched controls. We found TBX2 hypermethylation was associated with increased HCC risk, with ORs (95% CI) of 3.2 (1.8-6.0). The associations were mainly among high-risk subjects; among subjects infected with HBV/HCV, the OR (95% CI) of TBX2 methylation was 5.3 (2.2-12.7). Among subjects with high risk scores, the ORs (95% CIs) were 7.8 (1.5-38.6) for Wen-HCC model ≥16, 5.8 (2.2-15.5) for Hung-HCC ≥15 and 7.5 (2.2-26.0) for Michikawa-HCC ≥8. Adding TBX2 methylation improved the accuracy of risk models for a high-risk population, with the area under the curve (AUC) of 76% for Wen-HCC score with TBX2 methylation compared with 69% with Wen-HCC alone. The AUCs were 63% for Hung-HCC score plus TBX2 methylation, and 53% for Hung-HCC alone, 65% for Michikawa-HCC score plus TBX2 methylation and 58% for Michikawa-HCC alone. Our findings suggest the potential increase in risk assessment discrimination and accuracy from incorporation of DNA methylation. |
| Databáze: | OpenAIRE |
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