Is serum level of methylated RASSF1A valuable in diagnosing hepatocellular carcinoma in patients with chronic viral hepatitis C?

Mohamed, Nadia A.; Swify, Eman M.; Amin, Nabila F.; Soliman, Mona; Tag-Eldin, Lubna M.; Elsherbiny, Nahla M

doi:10.1016/j.ajg.2012.06.009

Cited by 41 publications

(39 citation statements)

References 30 publications

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“…In concordance with Chan et al (12 ) who reported the presence of methylated RASSF1A in 8% of the healthy volunteers using realtime PCR after digestion with a methylation-sensitive restriction enzyme. More recently, Mohamed et al (34) detected methylated RASSF1A in 10% of the controls . In a study by Dumache et al, (40) , hypermethylation of the GSTP1 gene was detected in 10.6% of control plasma samples.…”

Section: Zhang Et Al (33)mentioning

confidence: 98%

“…Chan et al (12) revealed that hypermethylated RASSF1A was found in the sera of 93% HCC patients, 58% HBV carriers, and 8% of normal volunteers. Mohamed et al (34) found that methylated RASSF1A was detected in 10% of the controls (2/20), 62.5% of the HCV group (25/40) and in 90% of the HCC group (36/40).Their positive ratios of RASSF1A was higher than ours .The different target CpG cites may be the major reason for the difference in detection ratio or it may be attributed to the difference in the technique used where we used methylation-specific PCR, while they used the combination of methylation-sensitive restrictionenzyme digestion and real-time PCR detection.…”

Section: Zhang Et Al (33)mentioning

confidence: 99%

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Evaluation of Hypermethylation of Ras Association Domain Family-1 a and Glutathione S-Transferase Protein-1 Genes as Diagnostic Marker for Hepatocellular Carcinoma

El-Sabakawy

Assaf

Arafa

et al. 2015

Zagazig University Medical Journal

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Background and study aims: The molecular pathogenesis of HCC involves well-defined genetic and epigenetic alterations. The Ras association domain family 1A (RASSF1A) and the Glutathione S-transferase P 1 (GSTP1) genes are two tumour suppressor genes that are reported to be silenced by CpG island promoter hypermethylation which is a key to the tumourigenic process in HCC. The aim of this study was to analyze the methylation frequency of RASSF1A and GSTP1 genes in early stages of HCC , chronic hepatitis C and healthy subjects to evaluate its value as a diagnostic marker for early HCC. Patients and methods: Methylation-specific polymerase chain reaction (MSP) was used to detect RASSF1A and GSTP1 promotor methylation in DNA extracted from plasma samples of 25 patients with HCC, 25 patients with chronic hepatitis C and 25 healthy controls. Assessment of alpha fetoprotein (AFP) was performed in all groups by ELISA using commercially available kits. Results: Methylated RASSF1A was detected in 76 % of the HCC group (19/25), in 20% of the chronic hepatitis C patients (5/25) and in 16% of the healthy controls(4/25). The methylation frequencies were significantly higher in patients with HCC compared to the controls (P ≤ 0.001) and chronic hepatitis C patients ( P ≤ 0.001). While methylated GSTP1 was detected in 44% of the HCC group(11/25) ,in 12% of the chronic hepatitis C group (3/25) and in 8% of the controls (2/25). Although the sensitivity and specificity, for each gene as an epigenetic biomarker was moderate (76% and 44% for RASSF1A and GSTP1 respectively), the combination analysis of both genes resulted in an increased sensitivity and specificity to 88%,and 76% respectively) in discriminating HCC from normal control and chronic hepatitis C pateints. As regard AFP, Receiver operating characteristic curves were plotted and showed an optimal cutoff value of 9.5 ng/ml with sensitivity of 88 % and specificity of 58% when the area under the receiver operator characteristic (AUROC) curve was 0.87 with 95% Confidence Interval .Conclusion: The epigenetic changes observed in this study indicate that examination of methylation status of RASSF1A and GSTP1 could be of value for early diagnosis of HCC especially when using a combination of more than one epigenetic marker .

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Section: Zhang Et Al (33)mentioning

confidence: 98%

Section: Zhang Et Al (33)mentioning

confidence: 99%

Evaluation of Hypermethylation of Ras Association Domain Family-1 a and Glutathione S-Transferase Protein-1 Genes as Diagnostic Marker for Hepatocellular Carcinoma

El-Sabakawy

Assaf

Arafa

et al. 2015

Zagazig University Medical Journal

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“…For example, the Ras association domain family protein 1A (RASSF1A) is a tumor suppressor that is frequently lost in human cancers by promoter-specific methylation. Mohamed, N. A et al [89] showed that RASSF1A gene hypermethylation could be detected in the serum of 90% of HCC patients and 62.5% of HCV patients, while only 10% of healthy volunteers displayed hypermethylation at this gene. Logistic regression analysis further identified that serum levels of methylated RASSF1A could be used to differentiate HCC patients from healthy volunteers, with an area under the receiver operating characteristics curve (AUROC) of 0.83 nmol/l and overall predictive accuracy of 77.5%.…”

Section: Introductionmentioning

confidence: 99%

Clinical applications of liquid biopsy as prognostic and predictive biomarkers in hepatocellular carcinoma: circulating tumor cells and circulating tumor DNA

Han

et al. 2018

J Exp Clin Cancer Res

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Hepatocellular carcinoma (HCC) is a highly malignant disease with a poor prognosis and high mortality due to a low early diagnosis rate, resistance to systemic treatments and progression to late-stage liver disease. Owing to limitations in the detection of HCC and the lack of awareness of healthcare systems, fewer than 40% of HCC patients are eligible for surgery due to advanced stages of the disease at the time of diagnosis and the occurrence of multiple lesions in the cirrhotic or fibrotic liver. At present, the updated American Association for the Study of Liver Disease (AASLD) guidelines no longer recommend alpha-fetoprotein (AFP) testing as a part of diagnostic evaluation. Thus, it is imperative to establish a novel diagnostic strategy with high sensitivity and reliability to monitor risk factors to detect HCC at an early stage. In recent years, “liquid biopsy,” (including circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA)), has emerged as a technique for the characterization of circulating cells, providing a strong basis for the individualized treatment of patients. As a noninvasive detection method, liquid biopsy is expected to play an important role in the early diagnosis, dynamic monitoring of cancer patients and drug screening. In this review, we will focus on the clinical applications, recent studies and future prospects of liquid biopsy, particularly focusing on HCC.

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“…Changes of DNA mutations could play an important role in the carcinogenesis process [79][80][81][82] . By now, several studies confirmed that TP53, EFGR, KRAS and APC are genes with common tumor specific mutations.…”

Section: Cell-free Tumor Associated Dnamentioning

confidence: 99%

Performance of different biomarkers for the management of hepatocellular carcinoma

Rojas¹,

Sánchez‐Torrijos²,

Gil‐Gómez³

et al. 2018

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Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the second cause of cancer related death due to latent liver disease, late diagnosis and non-available therapeutic treatment. Liver biopsy is still the gold standard in order to know the molecular biology of the tumor, its behaviour and invasive characteristics. Conventional diagnosis methods for HCC detection include imaging and serological tests with low sensitivity and specificity. In this review, we focus on the potential utility of certain serum biomarkers and a new approach, "liquid biopsy", in the management of HCC patients.

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Is serum level of methylated RASSF1A valuable in diagnosing hepatocellular carcinoma in patients with chronic viral hepatitis C?

Cited by 41 publications

References 30 publications

Evaluation of Hypermethylation of Ras Association Domain Family-1 a and Glutathione S-Transferase Protein-1 Genes as Diagnostic Marker for Hepatocellular Carcinoma

Evaluation of Hypermethylation of Ras Association Domain Family-1 a and Glutathione S-Transferase Protein-1 Genes as Diagnostic Marker for Hepatocellular Carcinoma

Clinical applications of liquid biopsy as prognostic and predictive biomarkers in hepatocellular carcinoma: circulating tumor cells and circulating tumor DNA

Performance of different biomarkers for the management of hepatocellular carcinoma

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