Special Issue "Biomarkers in Hepatocellular Carcinoma"

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (30 June 2021).

Special Issue Editors

Prof. Dr. Lory Saveria Croce'
E-Mail Website
Guest Editor
Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy
Interests: NAFLD; NASH; HCV; ALD; liver cirrhosis; HCC; portal hypertension; elastography
Dr. Mauro Giuffrè
E-Mail Website
Guest Editor
Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy
Interests: liver cirrhosis; HCC; portal hypertension; esophageal varices; liver elastography; spleen elastography

Special Issue Information

Dear Colleagues,

Hepatocellular Carcinoma (HCC) is the sixth most common cancer and the third cancer-related cause of death, with more than 800,000-related deaths each year.  In such a complicated scenario, tools for early diagnosis and prognosis prediction are fundamental for patient stratification.

HCC early diagnosis is currently achieved by ultrasound screening in cirrhotic patients, accompanied by evaluation in alpha-fetoprotein (AFP) fluctuation over time. However, this screening strategy is far from perfect, especially considering that even patients with liver disease and without advanced fibrosis can develop HCC. 

With advances in the understanding of tumor biology, along with the development of cellular and molecular techniques, the use of biomarkers related to early detection, invasiveness, metastasis, and recurrence have attracted a great deal of investigative interest resulting in the identification and utilization of several novel markers in this disease. This Special Issue will address the current advances in biomarkers in HCC.

Prof. Dr. Lory Saveria Croce'
Dr. Mauro Giuffrè
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Diagnostics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Liver
  • Liver Cirrhosis
  • Hepatocellular Carcinoma
  • HCC
  • Biomarkers
  • Diagnostic Biomarkers
  • Prognostic Biomarkers
  • Early Diagnosis

Published Papers (3 papers)

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Research

Article
The Relevance of SOCS1 Methylation and Epigenetic Therapy in Diverse Cell Populations of Hepatocellular Carcinoma
Diagnostics 2021, 11(10), 1825; https://doi.org/10.3390/diagnostics11101825 - 02 Oct 2021
Viewed by 394
Abstract
The suppressor of cytokine signaling 1 (SOCS1) is a tumor suppressor gene found to be hypermethylated in cancers. It is involved in the oncogenic transformation of cirrhotic liver tissues. Here, we investigated the clinical relevance of SOCS1 methylation and modulation upon [...] Read more.
The suppressor of cytokine signaling 1 (SOCS1) is a tumor suppressor gene found to be hypermethylated in cancers. It is involved in the oncogenic transformation of cirrhotic liver tissues. Here, we investigated the clinical relevance of SOCS1 methylation and modulation upon epigenetic therapy in diverse cellular populations of hepatocellular carcinoma (HCC). HCC clinical specimens were evaluated for SOCS1 methylation and mRNA expression. The effect of 5-Azacytidine (5-AZA), a demethylation agent, was assessed in different subtypes of HCC cells. We demonstrated that the presence of SOCS1 methylation was significantly higher in HCC compared to peri-HCC and non-tumoral tissues (52% vs. 13% vs. 14%, respectively, p < 0.001). In vitro treatment with a non-toxic concentration of 5-AZA significantly reduced DNMT1 protein expression for stromal subtype lines (83%, 73%, and 79%, for HLE, HLF, and JHH6, respectively, p < 0.01) compared to cancer stem cell (CSC) lines (17% and 10%, for HepG2 and Huh7, respectively), with the strongest reduction in non-tumoral IHH cells (93%, p < 0.001). 5-AZA modulated the SOCS1 expression in different extents among the cells. It was restored in CSC HCC HepG2 and Huh7 more efficiently than sorafenib. This study indicated the relevance of SOCS1 methylation in HCC and how cellular heterogeneity influences the response to epigenetic therapy. Full article
(This article belongs to the Special Issue Biomarkers in Hepatocellular Carcinoma)
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Article
Detection of CTNNB1 Hotspot Mutations in Cell-Free DNA from the Urine of Hepatocellular Carcinoma Patients
Diagnostics 2021, 11(8), 1475; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11081475 - 14 Aug 2021
Viewed by 499
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. The beta-catenin gene, CTNNB1, is among the most frequently mutated in HCC tissues. However, mutational analysis of HCC tumors is hampered by the difficulty of obtaining tissue samples using traditional biopsy. Here, [...] Read more.
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. The beta-catenin gene, CTNNB1, is among the most frequently mutated in HCC tissues. However, mutational analysis of HCC tumors is hampered by the difficulty of obtaining tissue samples using traditional biopsy. Here, we explored the feasibility of detecting tumor-derived CTNNB1 mutations in cell-free DNA (cfDNA) extracted from the urine of HCC patients. Using a short amplicon qPCR assay targeting HCC mutational hotspot CTNNB1 codons 32–37 (exon 3), we detected CTNNB1 mutations in 25% (18/73) of HCC tissues and 24% (15/62) of pre-operative HCC urine samples in two independent cohorts. Among the CTNNB1-mutation-positive patients with available matched pre- and post-operative urine (n = 13), nine showed apparent elimination (n = 7) or severalfold reduction (n = 2) of the mutation in urine following tumor resection. Four of the seven patients with no detectable mutations in postoperative urine remained recurrence-free within five years after surgery. In contrast, all six patients with mutation-positive in post-operative urine recurred, including the two with reduced mutation levels. This is the first report of association between the presence of CTNNB1 mutations in pre- and post-operative urine cfDNA and HCC recurrence with implications for minimum residual disease detection. Full article
(This article belongs to the Special Issue Biomarkers in Hepatocellular Carcinoma)
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Article
Chemerin Is a Valuable Biomarker in Patients with HCV Infection and Correlates with Liver Injury
Diagnostics 2020, 10(11), 974; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10110974 - 19 Nov 2020
Cited by 4 | Viewed by 762
Abstract
Hepatitis C virus (HCV)-induced inflammation contributes to progressive liver disease. The chemoattractant protein chemerin is associated with systemic inflammation. We hypothesized that chemerin is a biomarker that predicts the severity of liver disease in HCV patients. Furthermore, we investigated whether serum chemerin levels [...] Read more.
Hepatitis C virus (HCV)-induced inflammation contributes to progressive liver disease. The chemoattractant protein chemerin is associated with systemic inflammation. We hypothesized that chemerin is a biomarker that predicts the severity of liver disease in HCV patients. Furthermore, we investigated whether serum chemerin levels change during the course of HCV treatment using direct-acting antivirals (DAAs). Therefore, we measured serum concentration of chemerin in a cohort of 82 HCV-infected patients undergoing DAA treatment. Serum chemerin was positively associated with leukocyte count and negatively with markers of hepatic function and the model of end-stage liver disease (MELD) score. Low circulating chemerin levels significantly correlated with advanced liver fibrosis and cirrhosis as measured by the fibrosis-4 (FIB-4) score, the aminotransferase/platelet (AST/PLT) ratio index (APRI) score and the non-alcoholic fatty liver disease (NAFLD) score. Chemerin did not correlate with viral load or viral genotype. Treatment with DAAs did not improve MELD score and leukocyte count within the observation period, up to three months after the end of DAA treatment. Accordingly, chemerin levels remained unchanged during the treatment period. We conclude that low circulating chemerin is a noninvasive biomarker for hepatic dysfunction and advanced liver fibrosis and cirrhosis in HCV infection. Full article
(This article belongs to the Special Issue Biomarkers in Hepatocellular Carcinoma)
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