Advances in hepatocellular carcinoma: hepatocarcinogenesis, role of exosomal noncoding RNAs, and diagnostic pathology
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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 [8] 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.
Funding
None.