Journal of Liver Cancer

Original Article

Identification of new biomarkers of hepatic cancer stem cells through proteomic profiling: Sung Hoon Choi, Ha Young Lee, Sung Ho Yun, Sung Jae Jang, Seung Up Kim, Jun Yong Park, Sang Hoon Ahn, Do Young Kim; Received December 23, 2024 Accepted March 8, 2025 Published online March 20, 2025; DOI: https://doi.org/10.17998/jlc.2025.03.08 [Accepted]

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Abstract PDF: Background
In hepatocellular carcinoma (HCC), which exhibits high mortality and recurrence rates globally, the traits of cancer stem cells that significantly influence recurrence and metastasis are not well understood. Cancer stem cells (CSCs) are self-renewing cell types identified in most liquid and solid cancers, contributing to tumor initiation, growth, resistance, recurrence, and metastasis following chemo-radiotherapy or trans-arterial chemoembolization therapy.
Methods
CSCs are classified based on the expression of cell surface markers such as CD133, which varies depending on the tumor type. Proteomic analysis of liver cancer cell lines with cancer stem cell potential and HCC cancer cell lines lacking stem cell propensity was conducted to compare and analyze specific expression patterns.
Results
Proteomic profiling and enrichment analysis revealed higher expression of the calcium-binding protein S100 family in CD133+ Huh7 cells than in neg or wild-type cells. Furthermore, elevated expression of S100 family members was confirmed in an actual CD133+ liver cancer cell line via protein-protein network analysis and qPCR.
Conclusion
The S100 family members are not only new markers of cancer stem cells but will also assist in identifying new treatment strategies for CSC metastasis and tumor advancement.

Review Article

Management of hepatocellular carcinoma in elderly and adolescent/young adult populations: Han Ah Lee; Received February 1, 2025 Accepted February 28, 2025 Published online March 20, 2025; DOI: https://doi.org/10.17998/jlc.2025.02.28 [Accepted]

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Abstract PDF: Hepatocellular carcinoma (HCC) presents unique challenges in both the elderly and adolescent/young adult (AYA) populations, requiring distinct management approaches. Recent epidemiological data show an increasing incidence of HCC in both age groups, with elderly cases rising significantly and AYA cases showing trends in specific regions. The clinical characteristics and treatment considerations vary substantially among these populations. Elderly patients with HCC typically present with hepatitis C virus infection, metabolic dysfunction-associated steatotic liver disease, well-differentiated tumors, and multiple comorbidities. In contrast, AYA patients with HCC often present with more aggressive tumor characteristics and predominantly with hepatitis B virus-related diseases. Treatment decisions for elderly patients with HCC require careful consideration of physiological reserves, comprehensive geriatric assessments, and potential complications. Recent studies have demonstrated that elderly patients can achieve outcomes comparable to younger patients across various treatment modalities when properly selected. While surgical outcomes are comparable to those of younger patients with proper selection, less-invasive options such as radiofrequency ablation or transarterial therapies may be more appropriate for some elderly patients. The treatment approach for AYA HCC emphasizes curative intent while considering long-term effects. AYA patients require specialized attention to their psychosocial needs, fertility preservation, and long-term health maintenance. Although data on AYA patients remain limited, they are known to have relatively favorable prognoses despite exhibiting more aggressive tumor characteristics. Management of HCC in both the elderly and AYA populations requires individualized approaches that consider age-specific factors. Both groups benefit from multidisciplinary team involvement and careful consideration of quality of life.

Editorial

Antitumor role of L-Arginine and argininosuccinate synthetase 1 in hepatocellular carcinoma: direct and immunological mechanisms: Hyuk Soo Eun; Received March 5, 2025 Accepted March 7, 2025 Published online March 11, 2025; DOI: https://doi.org/10.17998/jlc.2025.03.07 [Accepted]

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Review Articles

Insights into hepatocellular adenomas in Asia: molecular subtypes, clinical characteristics, imaging features, and hepatocellular carcinoma risks: Subin Heo, In Hye Song, Edouard Reizine, Maxime Ronot, Jean-Charles Nault, Hae Young Kim, Sang Hyun Choi, So Yeon Kim; Received February 7, 2025 Accepted March 6, 2025 Published online March 7, 2025; DOI: https://doi.org/10.17998/jlc.2025.03.06 [Accepted]

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Abstract PDF: Hepatocellular adenomas (HCAs) are benign monoclonal liver tumors. Advances in molecular studies have led to the identification of distinct subtypes of HCA with unique pathways, clinical characteristics, and complication risks, underscoring the need for precise diagnosis and tailored management. Malignant transformation and bleeding remain significant concerns. Imaging plays a crucial role in the identification of these subtypes, offering a non-invasive method to guide clinical decision-making. Most studies involving patients with HCAs have been conducted in Western populations; however, the number of studies focused on Asian population has increased in recent years. HCAs exhibit distinct features in Asian population, such as a higher prevalence among male patients and specific subtypes (e.g., inflammatory HCAs). Current clinical guidelines are predominantly influenced by Western data, which may not fully capture these regional differences in epidemiology and subtype distribution. Therefore, this review presents the updated molecular classification of HCAs and their epidemiologic differences between Asian and Western populations, and discuss the role of imaging techniques, particularly magnetic resonance imaging using hepatobiliary contrast agents, in classifying the subtypes and predicting the risk of hepatocellular carcinoma.

Epidemiology and genomic features of biliary tract cancer and its unique features in Korea: Seonjeong Woo, Youngun Kim, Sohyun Hwang, Hong Jae Chon; Received February 7, 2025 Accepted February 28, 2025 Published online March 4, 2025; DOI: https://doi.org/10.17998/jlc.2025.02.27 [Accepted]

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Abstract PDF: Biliary tract cancer (BTC) is a rare but highly aggressive malignancy that includes intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC), and gallbladder cancer (GBC). While BTC has a low global incidence, its regional variations are notable. Among nations, the Republic of Korea has the second-highest incidence of BTC globally, with the highest mortality rate worldwide, underscoring the need for a deeper understanding of this cancer. Liver fluke infection and hepatitis B virus (HBV) infection are key risk factors unique to Korea, contributing to regional differences in BTC incidence. Additionally, genomic alterations in Korean patients with BTC differ from those in other populations, including lower frequencies of IDH1 mutations and FGFR2 fusions in ICC and a higher prevalence of ERBB2 amplification in GBC. Recognizing the clinical significance of these alterations, ivosidenib and pemigatinib have been approved in Korea for BTC patients with IDH1 mutations and FGFR2 fusions, respectively. This review explores the epidemiology, risk factors, and molecular features of BTC, along with corresponding targeted therapies. Furthermore, we compare the unique characteristics of BTC in Korea with global data to inform future research and clinical practice.

Original Article

Hepatocellular Carcinoma in Korea: An Analysis of the 2016–2018 Korean Nationwide Cancer Registry: Jihyun An, Young Chang, Gwang Hyeon Choi, Won Sohn, Jeong Eun Son, Hyunjae Shin, Jae Hyun Yoon, Jun Sik Yoon, Hye Young Jang, Eun Ju Cho, Ji Won Han, Suk Kyun Hong, Ju-Yeon Cho, Kyu-Won Jung, Eun Hye Park, Eunyang Kim, Bo Hyun Kim; Received January 26, 2025 Accepted February 20, 2025 Published online March 4, 2025; DOI: https://doi.org/10.17998/jlc.2025.02.20 [Accepted]

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Abstract PDF: Background/Aims
Hepatocellular carcinoma (HCC) is the sixth most common cancer and second leading cause of cancer-related deaths in South Korea. This study evaluated the characteristics of Korean patients newly diagnosed with HCC in 2016–2018.
Methods
Data from the Korean Primary Liver Cancer Registry (KPLCR), a representative database of patients newly diagnosed with HCC in South Korea, were analyzed. This study investigated 4,462 patients with HCC registered in the KPLCR in 2016–2018.
Results
The median patient age was 63 (interquartile range, 55–72) years; 79.7% of patients were male. Hepatitis B infection was the most common underlying liver disease (54.5%). The Barcelona Clinic Liver Cancer (BCLC) staging system classified patients as follows: stage 0 (14.9%), A (28.8%), B (7.5%), C (39.0%), and D (9.8%). The median overall survival was 3.72 years (95% CI: 3.47–4.14), with 1-, 3-, and 5-year overall survival rates of 71.3%, 54.1%, and 44.3%, respectively. In 2016–2018, there was a significant shift toward BCLC stage 0–A and Child–Turcotte–Pugh liver function class A (Ps<0.05), although survival rates did not differ by diagnosis year. In the treatment group (n=4,389), the most common initial treatments were transarterial therapy (31.7%), surgical resection (24.9%), best supportive care (18.9%), and local ablation therapy (10.5%).
Conclusions
Between 2016 and 2018, HCC tended to be diagnosed at earlier stages, with better liver function in later years. However, since approximately half of the patients remained diagnosed at an advanced stage, more rigorous and optimized HCC screening strategies should be implemented.

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