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Cancers
Special Issues
Chronic Liver Disease and Hepatocellular Carcinoma Biomarkers
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Chronic Liver Disease and Hepatocellular Carcinoma Biomarkers

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 14921

Special Issue Editor

Dr. Filippo Oliveri

E-Mail Website
Guest Editor
Hepatology Unit, University Hospital of Pisa, via Paradisa n. 2, Pisa, Italy
Interests: hepatocellular carcinoma; HCC biomarkers; viral hepatitis

Special Issue Information

Dear Colleagues,

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide. HCC arises mainly in patients with chronic liver diseases, and cirrhosis represents the major risk condition for its development.

The HCC 1-year survival rate ranges widely from 10% to more than 90% depending on the baseline clinical stage. Early diagnosis is the most important determinant of survival, and HCC surveillance is based on highly operator-dependent ultrasonography (US) since the effectiveness of circulating biomarkers of HCC—such as alpha-fetoprotein (AFP) which is most used—is hampered by their low diagnostic accuracy.

Prognosis of HCC patients is linked to tumor and cirrhosis stages and performance status at diagnosis. The development of the Barcelona Clinic Liver Cancer (BCLC) staging system represents a milestone among the widely accepted staging systems for clinical decision making and stage-based treatment recommendations. However, histopathologic, genetic, and epigenetic HCC features as well as circulating biomarkers or liquid biopsy are not yet considered in the prognostic classifications. Treatment choices need to be individualized based on patient characteristics and preferences, particularly in advanced stage HCC, where systemic therapy is the standard of care. Circulating tumor biomarkers may be used to guide therapy; however, a distinction has to be made between prognostic markers, supposed to provide information about long-term outcome, and predictive markers of HCC response and survival.

Advanced HCC treatment is rapidly evolving, and in recent years, the availability of molecular targeted drugs is promoting the preselection of patients using drug-specific predictive biomarkers. Response to locoregional treatments and systemic therapies can currently be monitored simply using digital imaging and, thus, the AI-driven physics and mathematical models of the kinetics of different biomarkers may represent a new challenge for the amelioration of clinical monitoring and therapy individualization.

The aim of this Special Issue is to present original contributions and updated reviews on HCC biomarkers as provided by genomics, epigenomics, transcriptomics, proteomics, and other omics platforms which propose and discuss new or optimized tools for surveillance, early diagnosis, and individualization of the clinical management and treatment of HCC.

Dr. Filippo Oliveri
Guest Editor

Manuscript Submission Information

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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. Cancers is an international peer-reviewed open access semimonthly 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 2900 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

  • hepatocellular carcinoma (HCC)
  • cirrhosis
  • surveillance
  • diagnosis
  • prognosis
  • predictive factors
  • biomarkers
  • liquid biopsy

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Published Papers (4 papers)

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Research

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14 pages, 3676 KiB  
Article
Clinical Significance of Glycolytic Metabolic Activity in Hepatocellular Carcinoma
by Joann Jung, Sowon Park, Yeonwoo Jang, Sung-Hwan Lee, Yun Seong Jeong, Sun Young Yim and Ju-Seog Lee
Cancers 2023, 15(1), 186; https://doi.org/10.3390/cancers15010186 - 28 Dec 2022
Cited by 4 | Viewed by 2127
Abstract
High metabolic activity is a hallmark of cancers, including hepatocellular carcinoma (HCC). However, the molecular features of HCC with high metabolic activity contributing to clinical outcomes and the therapeutic implications of these characteristics are poorly understood. We aimed to define the features of [...] Read more.
High metabolic activity is a hallmark of cancers, including hepatocellular carcinoma (HCC). However, the molecular features of HCC with high metabolic activity contributing to clinical outcomes and the therapeutic implications of these characteristics are poorly understood. We aimed to define the features of HCC with high metabolic activity and uncover its association with response to current therapies. By integrating gene expression data from mouse liver tissues and tumor tissues from HCC patients (n = 1038), we uncovered three metabolically distinct HCC subtypes that differ in clinical outcomes and underlying molecular biology. The high metabolic subtype is characterized by poor survival, the strongest stem cell signature, high genomic instability, activation of EPCAM and SALL4, and low potential for benefitting from immunotherapy. Interestingly, immune cell analysis showed that regulatory T cells (Tregs) are highly enriched in high metabolic HCC tumors, suggesting that high metabolic activity of cancer cells may trigger activation or infiltration of Tregs, leading to cancer cells’ evasion of anti-cancer immune cells. In summary, we identified clinically and metabolically distinct subtypes of HCC, potential biomarkers associated with these subtypes, and a potential mechanism of metabolism-mediated immune evasion by HCC cells. Full article
(This article belongs to the Special Issue Chronic Liver Disease and Hepatocellular Carcinoma Biomarkers)
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12 pages, 822 KiB  
Article
Radiofrequency Ablation versus Transarterial Chemoembolization for Hepatocellular Carcinoma within Milan Criteria: Prognostic Role of Tumor Burden Score
by Shu-Yein Ho, Po-Hong Liu, Chia-Yang Hsu, Yi-Hsiang Huang, Jia-I Liao, Chien-Wei Su, Ming-Chih Hou and Teh-Ia Huo
Cancers 2022, 14(17), 4207; https://doi.org/10.3390/cancers14174207 - 30 Aug 2022
Cited by 4 | Viewed by 1735
Abstract
Tumor burden score (TBS), estimated by the diameter and number of tumor nodules, was recently proposed to assess the tumor burden in hepatocellular carcinoma (HCC). We aimed to evaluate the prognostic impact of TBS on HCC patients within the Milan criteria undergoing radiofrequency [...] Read more.
Tumor burden score (TBS), estimated by the diameter and number of tumor nodules, was recently proposed to assess the tumor burden in hepatocellular carcinoma (HCC). We aimed to evaluate the prognostic impact of TBS on HCC patients within the Milan criteria undergoing radiofrequency ablation (RFA) or transarterial chemoembolization (TACE). A total of 883 patients undergoing RFA and TACE were included. The multivariate Cox proportional hazards model was used to determine independent prognostic predictors in different patient cohorts. The TACE group had significantly higher TBS compared with the RFA group. The RFA group had better long-term survival than the TACE group in patients within the Milan criteria in univariate survival analysis. In the Cox model, serum α-fetoprotein (AFP) > 20 ng/mL, performance status 1–2, medium and high TBS, albumin–bilirubin (ALBI) grade 2 and grade 3 were independent predictors linked with mortality (all p < 0.001). Overall, TACE was not an independent predictor; among patients with low TBS, TACE was independently associated with decreased survival compared with RFA (p = 0.034). Conclusions: TBS is a feasible prognostic marker for HCC patients within the Milan criteria. TACE may be an effective treatment alternative for these patients. Among patients with low TBS, RFA should be considered the priority treatment modality. Full article
(This article belongs to the Special Issue Chronic Liver Disease and Hepatocellular Carcinoma Biomarkers)
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Review

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16 pages, 1431 KiB  
Review
Cell-Free DNA as a Surveillance Tool for Hepatocellular Carcinoma Patients after Liver Transplant
by Joao Manzi, Camilla O. Hoff, Raphaella Ferreira, Renata Glehn-Ponsirenas, Gennaro Selvaggi, Akin Tekin, Christopher B. O’Brien, Lynn Feun, Rodrigo Vianna and Phillipe Abreu
Cancers 2023, 15(12), 3165; https://doi.org/10.3390/cancers15123165 - 13 Jun 2023
Cited by 3 | Viewed by 2603
Abstract
The liver is the world’s sixth most common primary tumor site, responsible for approximately 5% of all cancers and over 8% of cancer-related deaths. Hepatocellular carcinoma (HCC) is the predominant type of liver cancer, accounting for approximately 75% of all primary liver tumors. [...] Read more.
The liver is the world’s sixth most common primary tumor site, responsible for approximately 5% of all cancers and over 8% of cancer-related deaths. Hepatocellular carcinoma (HCC) is the predominant type of liver cancer, accounting for approximately 75% of all primary liver tumors. A major therapeutic tool for this disease is liver transplantation. Two of the most significant issues in treating HCC are tumor recurrence and graft rejection. Currently, the detection and monitoring of HCC recurrence and graft rejection mainly consist of imaging methods, tissue biopsies, and alpha-fetoprotein (AFP) follow-up. However, they have limited accuracy and precision. One of the many possible components of cfDNA is circulating tumor DNA (ctDNA), which is cfDNA derived from tumor cells. Another important component in transplantation is donor-derived cfDNA (dd-cfDNA), derived from donor tissue. All the components of cfDNA can be analyzed in blood samples as liquid biopsies. These can play a role in determining prognosis, tumor recurrence, and graft rejection, assisting in an overall manner in clinical decision-making in the treatment of HCC. Full article
(This article belongs to the Special Issue Chronic Liver Disease and Hepatocellular Carcinoma Biomarkers)
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22 pages, 1450 KiB  
Review
Biomarkers and Genetic Markers of Hepatocellular Carcinoma and Cholangiocarcinoma—What Do We Already Know
by Jacek Baj, Łukasz Bryliński, Filip Woliński, Michał Granat, Katarzyna Kostelecka, Piotr Duda, Jolanta Flieger, Grzegorz Teresiński, Grzegorz Buszewicz, Marzena Furtak-Niczyporuk and Piero Portincasa
Cancers 2022, 14(6), 1493; https://doi.org/10.3390/cancers14061493 - 15 Mar 2022
Cited by 15 | Viewed by 7489
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer with an increasing worldwide mortality rate. Cholangiocarcinoma (CCA) is the second most common primary liver cancer. In both types of cancers, early detection is very important. Biomarkers are a relevant part of diagnosis, [...] Read more.
Hepatocellular carcinoma (HCC) is the most common primary liver cancer with an increasing worldwide mortality rate. Cholangiocarcinoma (CCA) is the second most common primary liver cancer. In both types of cancers, early detection is very important. Biomarkers are a relevant part of diagnosis, enabling non-invasive detection and control of cancer recurrence, as well as in the application of screening tests in high-risk groups. Furthermore, some of these biomarkers are useful in controlling therapy and treatment selection. Detection of some markers presents higher sensitivity and specificity in combination with other markers when compared with a single detection. Some gene aberrations are also prognostic markers in the two types of cancers. In the following review, we discuss the most common biomarkers and genetic markers currently being used in the diagnosis of hepatocellular carcinoma and cholangiocarcinoma. Full article
(This article belongs to the Special Issue Chronic Liver Disease and Hepatocellular Carcinoma Biomarkers)
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