Advances in hepatocellular carcinoma: hepatocarcinogenesis, role of exosomal noncoding RNAs, and diagnostic pathology

doi:10.12701/jyms.2024.01221

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Editorial Advances in hepatocellular carcinoma: hepatocarcinogenesis, role of exosomal noncoding RNAs, and diagnostic pathology: Joon Hyuk Choi; DOI: https://doi.org/10.12701/jyms.2024.01221
Published online: November 7, 2024

Department of Pathology, Yeungnam University College of Medicine, Daegu, Korea

Corresponding author: Joon Hyuk Choi, MD, PhD Department of Pathology, Yeungnam University College of Medicine, 170 Hyeonchung-ro, Namgu, Daegu 42415, Korea Tel: +82-53-640-6754 • Fax: +82-53-640-6769 • E-mail: joonhyukchoi@ynu.ac.kr

• Received: October 17, 2024 • Accepted: October 21, 2024

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Hepatocellular carcinoma (HCC) is a primary liver malignancy composed of epithelial cells that exhibit hepatocellular differentiation. HCC accounts for 75% to 85% of all primary liver cancers [1]. Globally, primary liver cancer is the sixth most common cancer and the third leading cause of cancer-related deaths, following lung and colorectal cancers, with an estimated 865,269 new cases and 757,948 deaths in 2022 [2]. Despite continuous advancements in the understanding and treatment of HCC [3,4], its diagnosis and management remain challenging because of its histological and molecular heterogeneity, which results in persistently high mortality rates.

This special issue on HCC presents a collection of articles with particular focus on the cellular origins of liver cancer stem cells (CSCs), exosomal noncoding RNAs (ncRNAs), and advancements in diagnostic pathology.

Eun [5] has provided an in-depth discussion of hepatocarcinogenesis, focusing on the cellular origins of liver CSCs. Heterogeneity in HCCs has been attributed to the diverse cellular origins of liver CSCs. This review explores the normal physiology of liver regeneration and offers a comprehensive overview of hepatocarcinogenesis, including cancer initiation, isolation of liver CSCs, key molecular signaling pathways, and the role of microRNAs (miRNAs). In addition, Eun reviews the cellular origins of liver CSCs, highlighting the roles of hematopoietic and mesenchymal stem cells, along with the more widely recognized hepatocytes and hepatic progenitor cells.

Yoo and Kang [6] have explored the clinical significance of exosomal ncRNAs in HCC. These ncRNAs, encapsulated within exosomes, are classified as miRNAs, long ncRNAs (lncRNAs), and circular RNAs (circRNAs). This review highlights the clinical applications of HCC-derived exosomal miRNAs, lncRNAs, and circRNAs as diagnostic, prognostic, and therapeutic biomarkers for HCC. Although research on the therapeutic and biomarker potentials of exosomal RNAs is still at an early stage, this review highlights the need for further research in this promising area [7].

Choi and Thung [8] have explored pathological and diagnostic approaches for well-differentiated hepatocellular lesions (WDHLs). These lesions include focal nodular hyperplasia, hepatocellular adenoma (HCA), macroregenerative nodule, dysplastic nodule, and well-differentiated HCC. The accurate classification of WDHLs is challenging, particularly in core needle biopsies. This review provides a comprehensive summary of the clinical, gross, and histological characteristics of WDHLs, along with insights into the use of specific stains and immunohistochemistry. Choi and Thung also explore the subtypes and molecular characteristics of HCA, highlighting the key immunohistochemical markers used to differentiate between benign and malignant hepatocellular tumors.

I would like to express my sincere gratitude to all authors and the Editorial Board of the Journal of Yeungnam Medical Science for the opportunity to edit this special issue on HCC. The biology and treatment of HCC encompass a dynamic and rapidly evolving field. A multidisciplinary approach involving oncologists, hepatologists, pathologists, and researchers is crucial to address the challenges of early detection, treatment resistance, and heterogeneity of tumor behavior. This special issue will prove valuable to clinicians and scientists dedicated to advancing HCC treatment and research.

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Conflicts of interest

Joon Hyuk Choi has been an editorial board member of Journal of Yeungnam Medical Science since 2002. He was not involved in the review process of this manuscript. There are no other conflicts of interest to declare.

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None.

References

1. Torbenson M, Ng IO, Park YN, Roncalli M, Sakamoto M. Hepatocellular carcinoma. In: The WHO Classification of Tumours Editorial Board, editor. WHO Classification of Tumours: Digestive System Tumours, 5th ed. Lyon, France: IARC Press; 2019. p. 229–30.
2. Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2024;74:229–63.Article PubMed
3. Llovet JM, Kelley RK, Villanueva A, Singal AG, Pikarsky E, Roayaie S, et al. Hepatocellular carcinoma. Nat Rev Dis Primers 2021;7:6.Article PubMed PDF
4. Choi JH, Thung SN. Advances in histological and molecular classification of hepatocellular carcinoma. Biomedicines 2023;11:2582.Article PubMed PMC
5. Eun JR. Overview of hepatocarcinogenesis focusing on cellular origins of liver cancer stem cells: a narrative review. J Yeungnam Med Sci 2025 [Epub]. https://doi.org/10.12701/jyms.2024.01088.Article
6. Yoo JS, Kang MK. Clinical significance of exosomal noncoding RNAs in hepatocellular carcinoma: a narrative review. J Yeungnam Med Sci 2024 Feb 8 [Epub]. https://doi.org/10.12701/jyms.2023.01186.Article
7. Narang P, Shah M, Beljanski V. Exosomal RNAs in diagnosis and therapies. Noncoding RNA Res 2022;7:7–15.Article PubMed PMC
8. Choi JH, Thung SN. Pathology and diagnostic approaches to well-differentiated hepatocellular lesions: a narrative review. J Yeungnam Med Sci 2025 [Epub]. https://doi.org/10.12701/jyms.2024.00766.Article

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Advances in hepatocellular carcinoma: hepatocarcinogenesis, role of exosomal noncoding RNAs, and diagnostic pathology