Diagnostic Value of the Methylation of Multiple Gene Promoters in Serum in Hepatitis B Virus-Related Hepatocellular Carcinoma

Abstract

This study sought to evaluate the diagnostic value of the methylation of multiple gene promoters in serum in hepatitis B virus- (HBV-) related hepatocellular carcinoma (HCC). A total of 343 participants were enrolled, including 98 patients with HCC, 75 patients with liver cirrhosis (LC), 90 patients with chronic hepatitis B (CHB), and 80 healthy individuals. RASSF1A, APC, BVES, TIMP3, GSTP1, and HOXA9 were selected as the candidate genes. The MethyLight method was used to assay promoter methylation statuses. The diagnostic performances of markers were assessed by constructing receiver operating characteristic (ROC) curves. The prevalences of methylation for RASSF1A, APC, BVES, HOXA9, GSTP1, and TIMP3 were 52.04%, 36.73%, 29.59%, 20.41%, 17.35%, and 11.22%, respectively. APC methylation completely overlapped with RASSF1A methylation. The area under the curve (AUC) for RASSF1A methylation (0.718) was better than the corresponding AUC for AFP (0.609) in distinguishing HCC from CHB. When RASSF1A, BVES, HOXA9, and AFP were combined, the AUC was 0.852 (95% CI = 0.796–0.908, P = 0.028), and the sensitivity and specificity were 83.7% and 78.9%, respectively. In conclusion, an assay that combines methylation of the RASSF1A, BVES, and HOXA9 gene promoters in serum and AFP could significantly improve HBV-related HCC diagnoses.

Using circulating tumor DNA as a novel biomarker to screen and diagnose hepatocellular carcinoma: A systematic review and meta‐analysis

“…Among these 33 publications, 11 articles described the diagnostic role of circulating Ras association domain family 1 isoform A ( RASSF1A ) methylation in HCC and eight articles evaluated the diagnostic performance of ctDNA combined with AFP assay in HCC . Nine articles assessed the diagnostic accuracy of AFP assay for HCC …”

Association of GSTP1 and P16 promoter methylation with the risk of HBV-related hepatocellular carcinoma: a meta-analysis

“… 15 , 16 , 18 , 19 However, there are contradictory results concerning the role of GSTP1 promoter methylation in the progression of HBV-related HCC as well. 17 , 20 In view of the conflicting evidence on this issue, we performed this meta-analysis to evaluate the exact relationship between GSTP1 promoter methylation and increased risk of HBV-related HCC. Consequently, our results confirmed that the methylation rates of GSTP1 gene in cancer tissues were considerably higher than those of normal controls (OR =6.05, 95% CI =1.20–30.52) as well as cirrhosis tissues (OR =5.21, 95% CI =2.19–12.41), suggesting the importance of GSTP1 promoter region methylation in the development of HBV-related HCC.…”

Potential of the use of methylation biomarkers for diagnostics and prognosis of hepatocellular carcinoma in liquid biopsy

“…Так, определение уровня метилирования сайта в гене GSTP1 в ц-ДНК из сыворотки крови при инфекции HCV показало бόльшую специфичность (93,3 %) по сравнению с определением сывороточного АФП (72,7 %) для диагностики ГК [64]. В то же время для пациентов с HBV-ассоциированными ГК индивидуальная диагностическая значимость метилирования сайта в промоторе GSTP1 невысока [34]. Этот биомаркер может быть использован для диагностики ГК в составе мультигенных панелей: по данным W. Huang и соавт., такая мультигенная панель отличается более высоким показателем чувствительности (93,6 %) по сравнению с АФП (48,4 %) [56].…”

“…Гиперметилирование сайтов в промоторе гена RASSF1 в ц-ДНК из крови обладает высокой диагностической значимостью: показатели чувствительности и специфичности составляют 52-75 и 58,9-91,5 % соответственно [33,34,69]. В то же время диагностическая точность панелей биомаркеров метилирования, в состав которых входят сайты в промоторе гена RASSF1 (см.…”

“…В то же время диагностическая точность панелей биомаркеров метилирования, в состав которых входят сайты в промоторе гена RASSF1 (см. таблицу), превышает индивидуальные показатели этого биомаркера и характеризуется чувствительностью в диапазоне 73,5-84,0 % и специфичностью 91,1-94,0 % [34,55].…”