DNA Methylation and Micro-RNAs: The Most Recent and Relevant Biomarkers in the Early Diagnosis of Hepatocellular Carcinoma

Cozma, Angela; Fodor, Adriana; Vulturar, Romana; Sitar-Tăut, Adela-Viviana; Orășan, Olga Hilda; Mureșan, Flaviu; Login, Cezar; Suharoschi, Ramona

doi:10.3390/medicina55090607

Cited by 8 publications

(3 citation statements)

References 59 publications

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“…2b). To cover the CpGs associated with HCC as much as possible, other CpGs suitable for HCC detection were also included in our analysis, according to previous studies [29][30][31][32][33][34][35][36]. Finally, we designed a probe panel covering 1595 CpGs for subsequent analysis.…”

Section: Methylation Marker Selection and Targeted Em-seqmentioning

confidence: 99%

Hepatocellular carcinoma detection via targeted enzymatic methyl sequencing of plasma cell-free DNA

Guo

Zheng²,

et al. 2023

Clin Epigenet

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Background Epigenetic variants carried by circulating tumor DNA can be used as biomarkers for early detection of hepatocellular carcinoma (HCC) by noninvasive liquid biopsy. However, traditional methylation analysis method, bisulfite sequencing, with disadvantages of severe DNA damage, is limited in application of low-amount cfDNA analysis. Results Through mild enzyme-mediated conversion, enzymatic methyl sequencing (EM-seq) is ideal for precise determination of cell-free DNA methylation and provides an opportunity for HCC early detection. EM-seq of methylation control DNA showed that enzymatic conversion of unmethylated C to U was more efficient than bisulfite conversion. Moreover, a relatively large proportion of incomplete converted EM-seq reads contains more than 3 unconverted CH site (CH = CC, CT or CA), which can be removed by filtering to improve accuracy of methylation detection by EM-seq. A cohort of 241 HCC, 76 liver disease, and 279 normal plasma samples were analyzed for methylation value on 1595 CpGs using EM-seq and targeted capture. Model training identified 283 CpGs with significant differences in methylation levels between HCC and non-HCC samples. A HCC screening model based on these markers can efficiently distinguish HCC sample from non-HCC samples, with area under the curve of 0.957 (sensitivity = 90%, specificity = 97%) in the test set, performing well in different stages as well as in serum α-fetoprotein/protein induced by vitamin K absence-II negative samples. Conclusion Filtering of reads with ≥ 3 CHs derived from incomplete conversion can significantly reduce the noise of EM-seq detection. Based on targeted EM-seq analysis of plasma cell-free DNA, our HCC screening model can efficiently distinguish HCC patients from non-HCC individuals with high sensitivity and specificity.

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Section: Methylation Marker Selection and Targeted Em-seqmentioning

confidence: 99%

Hepatocellular carcinoma detection via targeted enzymatic methyl sequencing of plasma cell-free DNA

Guo

Zheng²,

et al. 2023

Clin Epigenet

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“…Few studies address the impact of NO production or NOS expression and changes in DNA methylation patterns. COX2 activity is enhanced by NOS2-derived NO, which promotes angiogenesis and cell differentiation [37][38][39] and tumor growth, invasion and metastasis potential [40][41][42]. Hence, the assessment of the correlation between COX2 and NOS2 expression and microvessel density in HCV-positive HCCs suggested its importance in the pathogenesis of the disease [43].…”

Section: No and Dna Methylationmentioning

confidence: 99%

Role of Nitric Oxide in Gene Expression Regulation during Cancer: Epigenetic Modifications and Non-Coding RNAs

Cruz‐Ojeda

Flores-Campos

Dios-Barbeito

et al. 2021

IJMS

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Nitric oxide (NO) has been identified and described as a dual mediator in cancer according to dose-, time- and compartment-dependent NO generation. The present review addresses the different epigenetic mechanisms, such as histone modifications and non-coding RNAs (ncRNAs), miRNA and lncRNA, which regulate directly or indirectly nitric oxide synthase (NOS) expression and NO production, impacting all hallmarks of the oncogenic process. Among lncRNA, HEIH and UCA1 develop their oncogenic functions by inhibiting their target miRNAs and consequently reversing the inhibition of NOS and promoting tumor proliferation. The connection between miRNAs and NO is also involved in two important features in cancer, such as the tumor microenvironment that includes key cellular components such as tumor-associated macrophages (TAMs), cancer associated fibroblasts (CAFs) and cancer stem cells (CSCs).

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“…Epigenetic alterations due to iron overload have also been implicated in hepatocarcinogenesis. Epigenetic defects such as increased DNA methylation commonly occur in HCC [114] . Lehmann et al [115] found 84% of the non-cancerous liver biopsies derived from HH patients exhibited hypermethylation of genes that are often hypermethylated in HCC.…”

Section: Mechanisms Of Iron Toxicity In Hh Leading To Hccmentioning

confidence: 99%

Association between hereditary hemochromatosis and hepatocellular carcinoma: a comprehensive review

Jayachandran¹,

Shrestha²,

Bridle³

et al. 2020

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Hepatocellular carcinoma (HCC) is a significant global health problem with high morbidity and mortality. Its incidence is increasing exponentially worldwide with a close overlap between annual incidence and death rates. Even though significant advances have been made in HCC treatment, fewer than 20% of patients with HCC are suitable for potentially curative treatment. Hereditary hemochromatosis (HH) is an important genetic risk factor for HCC. HH is an autosomal recessive disorder of iron metabolism, characterised by elevated iron deposition in most organs including the liver, leading to progressive organ dysfunction. HCC is a complication of HH, nearly always occurring in patients with cirrhosis and contributes to increased mortality rates. Identifying the susceptibility of development of HCC in HH patients has gained much traction. This review summarises the current knowledge with regard to the association of HH and HCC in order to encourage further research. In this review, we focus particularly on HFE gene-related HH. Herein, we highlight and discuss emerging clinical research which addresses the prevalence of HCC in HH patients and the coincidence of HH with other risk factors for HCC development. We also focus on the therapeutic tools in the management of HCC associated with HH.

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DNA Methylation and Micro-RNAs: The Most Recent and Relevant Biomarkers in the Early Diagnosis of Hepatocellular Carcinoma

Cited by 8 publications

References 59 publications

Hepatocellular carcinoma detection via targeted enzymatic methyl sequencing of plasma cell-free DNA

Hepatocellular carcinoma detection via targeted enzymatic methyl sequencing of plasma cell-free DNA

Role of Nitric Oxide in Gene Expression Regulation during Cancer: Epigenetic Modifications and Non-Coding RNAs

Association between hereditary hemochromatosis and hepatocellular carcinoma: a comprehensive review

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