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Biomedicines
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Hepatocellular Carcinoma: From Molecular Mechanisms to Novel Therapeutic Approaches
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Hepatocellular Carcinoma: From Molecular Mechanisms to Novel Therapeutic Approaches

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (30 September 2024) | Viewed by 11991

Special Issue Editor

Prof. Dr. Joon Hyuk Choi

E-Mail Website
Guest Editor
Department of Pathology, Yeungnam University College of Medicine, Daegu, Republic of Korea
Interests: hepatocellular carcinoma; primary liver cancer; precancerous conditions; carcinogen-esis; surgical pathology; biomarkers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue, “Hepatocellular Carcinoma: From Basic Research to Novel Therapeutic Approaches,” will focus on molecular findings, pathology, biomarkers, diagnostic imaging, clinical features, and novel therapeutic approaches relating to hepatocellular carcinoma (HCC).

HCC is the fourth leading cause of cancer-related death worldwide. It is a highly heterogeneous tumor at the molecular and pathological levels, and its incidence is increasing in Western countries. In the past decade, novel molecular findings, pathogenic mechanisms, and therapeutic targets have improved our understanding of HCC. Despite advances in many areas, the molecular pathogenesis of HCC has not been fully elucidated. The accurate diagnosis of HCC and therapeutic strategies remain challenging.

This Special Issue is open to basic and clinical research on HCC, as well as multidisciplinary approaches, and will cover original articles and reviews on the following topics: hepatocellular carcinoma, primary liver cancer, molecular biology, carcinogenesis, precancerous conditions, subtypes, biomarkers, diagnostic imaging, and novel therapeutic approaches.

Prof. Dr. Joon Hyuk Choi
Guest Editor

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 submissions that pass pre-check are 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. Biomedicines 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 2600 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
  • primary liver cancer
  • molecular biology
  • carcinogenesis
  • precancerous conditions
  • surgical pathology
  • biomarkers
  • diagnostic imaging
  • targeted therapy

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Published Papers (5 papers)

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Research

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14 pages, 3115 KiB  
Article
Reduced Lipid Peroxidation Predicts Unfavorable Prognosis in Hepatocellular Carcinoma, but Not Intrahepatic Cholangiocarcinoma
by Tiemo Sven Gerber, Hagen Roland Witzel, Arndt Weinmann, Fabian Bartsch, Mario Schindeldecker, Peter R. Galle, Hauke Lang, Wilfried Roth, Dirk Andreas Ridder and Beate Katharina Straub
Biomedicines 2023, 11(9), 2471; https://doi.org/10.3390/biomedicines11092471 - 6 Sep 2023
Cited by 1 | Viewed by 1358
Abstract
Primary liver cancer, including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), remains a significant contributor to cancer-related mortality worldwide. Oxidative stress and lipid peroxidation play a key role in chronic liver diseases and have been shown to be pivotal for tumor initiation and [...] Read more.
Primary liver cancer, including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), remains a significant contributor to cancer-related mortality worldwide. Oxidative stress and lipid peroxidation play a key role in chronic liver diseases and have been shown to be pivotal for tumor initiation and progression. 4-hydroxy-nonenal (4-HNE), one of the major mediators of oxidative stress and a well-established biomarker for lipid peroxidation, can act as a signal transducer, inducing inflammation and exerting carcinogenic effects. However, the role of 4-HNE in primary liver cancer remains poorly explored. In this study, we investigated 4-HNE levels in 797 liver carcinomas, including 561 HCC and 236 iCCA, by immunohistochemistry. We then correlated 4-HNE levels with comprehensive clinical data and survival outcomes. In HCC, lower expression levels of 4-HNE were associated with vascular invasion, a high tumor grade, a macrotrabecular-massive HCC subtype, and poor overall survival. Concerning iCCA, large duct iCCA showed significantly higher 4-HNE levels when compared to small duct iCCA. Yet, in iCCA, 4-HNE levels did not correlate with known prognostic parameters or survival outcomes. To conclude, in HCC but not in iCCA, low amounts of 4-HNE predict unfavorable survival outcomes and are associated with aggressive tumor behavior. These findings provide insights into the role of 4-HNE in liver cancer progression and may enable novel therapeutic strategies. Full article
(This article belongs to the Special Issue Hepatocellular Carcinoma: From Molecular Mechanisms to Novel Therapeutic Approaches)
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14 pages, 7346 KiB  
Article
Tumor-Associated Macrophages Affect the Tumor Microenvironment and Radioresistance via the Upregulation of CXCL6/CXCR2 in Hepatocellular Carcinoma
by Hsin-Lun Lee, Yi-Chieh Tsai, Narpati Wesa Pikatan, Chi-Tai Yeh, Vijesh Kumar Yadav, Ming-Yao Chen and Jo-Ting Tsai
Biomedicines 2023, 11(7), 2081; https://doi.org/10.3390/biomedicines11072081 - 24 Jul 2023
Cited by 3 | Viewed by 1968
Abstract
Background: Hepatocellular carcinoma is the sixth most diagnosed malignancy and the fourth most common cause of cancer-related mortality globally. Despite progress in the treatment of liver cancer, nonsurgical treatments remain unsatisfactory, and only 15% of early-stage cases are surgically operable. Radiotherapy (RT) is [...] Read more.
Background: Hepatocellular carcinoma is the sixth most diagnosed malignancy and the fourth most common cause of cancer-related mortality globally. Despite progress in the treatment of liver cancer, nonsurgical treatments remain unsatisfactory, and only 15% of early-stage cases are surgically operable. Radiotherapy (RT) is a non-surgical treatment option for liver cancer when other traditional treatment methods are ineffective. However, RT has certain limitations, including eliciting poor therapeutic effects in patients with advanced and recurrent tumors. Tumor-associated macrophages (TAMs) are major inflammatory cells in the tumor microenvironment that are key to tumor development, angiogenesis, invasion, and metastasis, and they play an essential role in RT responses. Methods: We used big data analysis to determine the potential of targeting CXCL6/CXCR2. We enrolled 50 patients with liver cancer who received RT at our hospital. Tumor tissue samples were examined for any relationship between CXCL6/CXCR2 activity and patient prognosis. Using a cell coculture system (Transwell), we cocultured Huh7 liver cancer cells and THP-1 monocytes with and without CXCL6/CXCR2 small interfering RNA for 72 h. Results: The overexpression of CXCL6/CXCR2 was highly correlated with mortality. Our tissue study indicated a positive correlation between CXCL6/CXCR2 and M2-TAMs subsets. The coculture study demonstrated that THP-1 monocytes can secrete CXCL6, which acts on the CXCR2 receptor on the surface of Huh7 cells and activates IFN-g/p38 MAPK/NF-κB signals to promote the epithelial–mesenchymal transition and radio-resistance. Conclusions: Modulating the TAM/CXCL6/CXCR2 tumor immune signaling axis may be a new treatment strategy for the effective eradication of radiotherapy-resistant hepatocellular carcinoma cells. Full article
(This article belongs to the Special Issue Hepatocellular Carcinoma: From Molecular Mechanisms to Novel Therapeutic Approaches)
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Review

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19 pages, 1681 KiB  
Review
The Biological Clock of Liver Metabolism in Metabolic Dysfunction-Associated Steatohepatitis Progression to Hepatocellular Carcinoma
by Pradeep Kumar Rajan, Utibe-Abasi S. Udoh, Robert Finley, Sandrine V. Pierre and Juan Sanabria
Biomedicines 2024, 12(9), 1961; https://doi.org/10.3390/biomedicines12091961 - 29 Aug 2024
Cited by 1 | Viewed by 911
Abstract
Circadian rhythms are endogenous behavioral or physiological cycles that are driven by a daily biological clock that persists in the absence of geophysical or environmental temporal cues. Circadian rhythm-related genes code for clock proteins that rise and fall in rhythmic patterns driving biochemical [...] Read more.
Circadian rhythms are endogenous behavioral or physiological cycles that are driven by a daily biological clock that persists in the absence of geophysical or environmental temporal cues. Circadian rhythm-related genes code for clock proteins that rise and fall in rhythmic patterns driving biochemical signals of biological processes from metabolism to physiology and behavior. Clock proteins have a pivotal role in liver metabolism and homeostasis, and their disturbances are implicated in various liver disease processes. Encoded genes play critical roles in the initiation and progression of metabolic dysfunction-associated steatohepatitis (MASH) to hepatocellular carcinoma (HCC) and their proteins may become diagnostic markers as well as therapeutic targets. Understanding molecular and metabolic mechanisms underlying circadian rhythms will aid in therapeutic interventions and may have broader clinical applications. The present review provides an overview of the role of the liver’s circadian rhythm in metabolic processes in health and disease, emphasizing MASH progression and the oncogenic associations that lead to HCC. Full article
(This article belongs to the Special Issue Hepatocellular Carcinoma: From Molecular Mechanisms to Novel Therapeutic Approaches)
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12 pages, 647 KiB  
Review
Machine Learning Combined with Radiomics Facilitating the Personal Treatment of Malignant Liver Tumors
by Liuji Sheng, Chongtu Yang, Yidi Chen and Bin Song
Biomedicines 2024, 12(1), 58; https://doi.org/10.3390/biomedicines12010058 - 26 Dec 2023
Cited by 3 | Viewed by 1593
Abstract
In the realm of managing malignant liver tumors, the convergence of radiomics and machine learning has redefined the landscape of medical practice. The field of radiomics employs advanced algorithms to extract thousands of quantitative features (including intensity, texture, and structure) from medical images. [...] Read more.
In the realm of managing malignant liver tumors, the convergence of radiomics and machine learning has redefined the landscape of medical practice. The field of radiomics employs advanced algorithms to extract thousands of quantitative features (including intensity, texture, and structure) from medical images. Machine learning, including its subset deep learning, aids in the comprehensive analysis and integration of these features from diverse image sources. This potent synergy enables the prediction of responses of malignant liver tumors to various treatments and outcomes. In this comprehensive review, we examine the evolution of the field of radiomics and its procedural framework. Furthermore, the applications of radiomics combined with machine learning in the context of personalized treatment for malignant liver tumors are outlined in aspects of surgical therapy and non-surgical treatments such as ablation, transarterial chemoembolization, radiotherapy, and systemic therapies. Finally, we discuss the current challenges in the amalgamation of radiomics and machine learning in the study of malignant liver tumors and explore future opportunities. Full article
(This article belongs to the Special Issue Hepatocellular Carcinoma: From Molecular Mechanisms to Novel Therapeutic Approaches)
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35 pages, 7932 KiB  
Review
Advances in Histological and Molecular Classification of Hepatocellular Carcinoma
by Joon Hyuk Choi and Swan N. Thung
Biomedicines 2023, 11(9), 2582; https://doi.org/10.3390/biomedicines11092582 - 20 Sep 2023
Cited by 4 | Viewed by 5569
Abstract
Hepatocellular carcinoma (HCC) is a primary liver cancer characterized by hepatocellular differentiation. HCC is molecularly heterogeneous with a wide spectrum of histopathology. The prognosis of patients with HCC is generally poor, especially in those with advanced stages. HCC remains a diagnostic challenge for [...] Read more.
Hepatocellular carcinoma (HCC) is a primary liver cancer characterized by hepatocellular differentiation. HCC is molecularly heterogeneous with a wide spectrum of histopathology. The prognosis of patients with HCC is generally poor, especially in those with advanced stages. HCC remains a diagnostic challenge for pathologists because of its morphological and phenotypic diversity. However, recent advances have enhanced our understanding of the molecular genetics and histological subtypes of HCC. Accurate diagnosis of HCC is important for patient management and prognosis. This review provides an update on HCC pathology, focusing on molecular genetics, histological subtypes, and diagnostic approaches. Full article
(This article belongs to the Special Issue Hepatocellular Carcinoma: From Molecular Mechanisms to Novel Therapeutic Approaches)
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