Analysis of DNA Methylation in Plasma for Monitoring Hepatocarcinogenesis

Huang, Wenyan; Li, Tong; Yang, Wenli; Chai, Xinjuan; Chen, Kefei; Wei, Ling; Duan, Shuwang; Li, Bo; Qin, Yang

doi:10.1089/gtmb.2014.0292

Cited by 23 publications

(28 citation statements)

References 39 publications

(46 reference statements)

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“…This finding is consistent with Araújo and Gioia et al [25,26] who reported an increase in RASSF1A PM with progression from regenerative conditions (e.g. cirrhosis) to hepatocellular nodules and HCC, as well as with Huang et al [15] and Chan et al [27] who reported RASSF1A methylation in the blood and tissues of HCC patients. Our results also showed an increasing frequency of p16 PM from NHT to HCC which is in agreement with the earlier studies [28,29].…”

Section: Normal Liver N = 13 (%) Chronic Hepatitis (Ch)supporting

confidence: 91%

“…The positive predictive value (PPV) was higher than the negative predictive value (NPV) for APC, FHIT, p16, and E-cadherin whereas, the negative predictive value was higher for p15 ( Table 1). Therefore, a previous study by Huang et al, [15] concluded that it may be useful to combine the plasma DNA methylation status of ELF, RASSF1A, p16, and GSTP1 with serum AFP for HCC screening and several studies had confirmed these data [16,17]. However controversial results were reported by Chang et al [18] who found no agreement between plasma and tissue DNA samples.…”

Section: Concordance Between Tissue and Plasma Dna Methylation In Hccmentioning

confidence: 99%

See 1 more Smart Citation

The Molecular Background Associated with the Progression of Hepatitis C to Hepatocellular Carcinoma

Zekri¹,

Bahnassy²,

Abdellateif³

2018

Hepatitis C - From Infection to Cure

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Hepatocellular carcinoma (HCC) is a major health problem worldwide. The DNA PM of cancer-related genes plays an important role in the development and progression of HCC. The data reported in our studies provide evidence that PM of p73, p14, and O6-MGMT is associated with HCC, whereas PM of the APC gene is more common in chronic hepatitis (CH) cases. Thus, it could be used as a maker for early detection of HCV-induced chronic active hepatitis. A panel of four genes APC, p73, p14, and O6-MGMT independently affected the classification of cases into HCC and CH with accuracy (89.9%), sensitivity (83.9%), and specificity (94.7%). Also, the detection of PM of APC, FHIT, p15, p16, and E-cadherin in peripheral blood of HCV-infected patients is a highly sensitive and specific. Therefore, blood could be used as efficiently as tissue biopsies to assess PM of different genes. This could help in the follow-up of CH patients and early detection of HCC. We did not observe a significant difference in the methylation status according to the virus type HBV versus HCV. So, plasma DNA is a reliable resource for methylation studies in the future, irrespective of the type of hepatitis infection.

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Section: Normal Liver N = 13 (%) Chronic Hepatitis (Ch)supporting

confidence: 91%

Section: Concordance Between Tissue and Plasma Dna Methylation In Hccmentioning

confidence: 99%

The Molecular Background Associated with the Progression of Hepatitis C to Hepatocellular Carcinoma

Zekri¹,

Bahnassy²,

Abdellateif³

2018

Hepatitis C - From Infection to Cure

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“…Анализ уровня метилирования сайтов в промоторах генов CDKN2A и CDKN2В в комбинации с другими биомаркерами метилирования в ц-ДНК из плазмы или сыворотки крови пациентов с ГК характеризуется высокими (84,0-93,6 %) показателями чувствительности для диагностики ГК [55,56]. Гиперметилирование сайтов в промоторе гена CDKN2A в ц-ДНК также рассматривается в качестве потенциального диагностического биомаркера, показатели чувствительности и специфичности которого составляют 47,8-73,0 и 82,6-87,2 % соответственно [54,57,58].…”

Section: обзорные статьиunclassified

“…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].…”

Section: обзорные статьиunclassified

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

2019

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Гепатоцеллюлярная карцинома (ГК)-самый распространенный тип рака печени, диагностируемый в основном на поздних стадиях. Применяемые в настоящее время в клинической практике молекулярные маркеры этого заболевания имеют недостаточную чувствительность для эффективной диагностики ГК, в связи с чем ведется активный поиск новых биомаркеров. Использование малоинвазивного метода жидкостной биопсии позволяет детектировать в биологических жидкостях пациентов специфические маркеры опухолевого роста, в частности характерное для ГК нарушение паттерна метилирования генов в ДНК, циркулирующей в крови. В настоящем обзоре рассмотрены наиболее перспективные для диагностики и прогноза биомаркеры метилирования, определяемые в циркулирующей ДНК крови пациентов с ГК.

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“…Numerous studies have confirmed that using DNA methylation changes as biomarkers for carcinoma is useful for early detection of cancer, including HCC [11]. For example, aberrant methylation of serum ELF, RASSF1A, GSTP1, APC, SFRP1, LINE-1, GRA has been shown to be useful as biomarkers for assessing the risk of HCC [12][13][14][15][16]. Abnormal hypermethylation of a CpG island in different stages of tumorigenesis is a dysfunction of tumor suppressor genes (TSGs) [17][18][19].…”

mentioning

confidence: 97%

Methylation of SOX1 and VIM promoters in serum as potential biomarkers for hepatocellular carcinoma

Liu¹,

Fan²,

Gao³

et al. 2017

neo

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Aberrant methylation of tumor-related genes has been identified as a promising biomarker for hepatocellular carcinoma (HCC). This study aimed to investigate the diagnostic value of SRY (sex determining region Y)-box 1 (SOX1) and Vimentin (VIM) promoter methylation for HCC. The study included 360 subjects, 240 patients with HCC, 29 with liver cirrhosis (LC), 66 with chronic hepatitis B (CHB) and 25 healthy controls (HCs). The methylation status of SOX1 and VIM promoters in the serum was detected by methylation-specific polymerase chain reaction (MSP). The methylation frequencies of SOX1 and VIM promoters in HCC patients were significantly higher than those in LC (p<0.001 and p<0.001), CHB (p<0.001 and p<0.001) and HC (p<0.001 and p<0.001) subjects. Furthermore, hypermethylation of SOX1 and VIM promoters were found in patients with advanced TNM stage (III-IV) and larger tumor size (≥5 cm) compared with early stage (I-II) (p<0.001 and p=0.004) patients with smaller tumor size (<3 cm) (p=0.018 and p=0.001). Moreover, the VIM promoter methylation frequency was higher in patients with portal vein tumor thrombosis (PVTT) (p=0.006) and vascular invasion (p=0.003). In addition, the combination of α-fetoprotein (≥20 ng/ml) with SOX1 and VIM promoter methylation significantly improved their diagnostic value. In conclusions, aberrant methylation of SOX1 and VIM promoters may be potential biomarkers for noninvasive detection of HCC and HCC metastasis.

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Analysis of DNA Methylation in Plasma for Monitoring Hepatocarcinogenesis

Abstract: These results suggested that the methylation of tumor suppressor genes may participate in the development and progression of HCC. Additionally, it may be useful to combine the plasma DNA methylation status of a panel of gene markers and the serum AFP for HCC screening.

Cited by 23 publications

References 39 publications

The Molecular Background Associated with the Progression of Hepatitis C to Hepatocellular Carcinoma

The Molecular Background Associated with the Progression of Hepatitis C to Hepatocellular Carcinoma

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

Methylation of SOX1 and VIM promoters in serum as potential biomarkers for hepatocellular carcinoma

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