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; J Liver Cancer. 2025;25(1):123-133. Published online March 20, 2025; DOI: https://doi.org/10.17998/jlc.2025.03.08

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Backgrounds/Aims
In hepatocellular carcinoma (HCC), which exhibits high mortality and recurrence rates globally, the traits of cancer stem cells (CSCs) that significantly influence recurrence and metastasis are not well understood. 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 CD133- 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 quantitative polymerase chain reaction (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.

Citations

Citations to this article as recorded by

Expression of liver cancer stem cell markers and association with recurrence and survival in hepatocellular carcinoma
Xing-Qing Jia, Shuai Han, Yan-Sheng Shang, Fan-Guo Kong, Lin Qi, Cheng-Liang Wang, Wu-Jun Xiong
World Journal of Stem Cells.2026;[Epub] CrossRef
Cancer stem cells in hepatocellular carcinoma: therapy resistance and emerging treatments
Dipesh Kumar Yadav, Rajesh Kumar Yadav, Alina Singh, Yi Huang, Dandan Bao, Zhangwei Yang, Hanzhang Huang, Yin Jiang, Pengwei Wang, Sisi Lin, Yongfei Hua, Yiren Hu
Frontiers in Immunology.2025;[Epub] CrossRef

Review Article

Update on Pathologic and Radiologic Diagnosis of Combined Hepatocellular-Cholangiocarcinoma: Hyungjin Rhee, Jae Hyon Park, Young Nyun Park; J Liver Cancer. 2021;21(1):12-24. Published online March 31, 2021; DOI: https://doi.org/10.17998/jlc.21.1.12

13,487 Views
390 Downloads
12 Citations

Abstract PDF

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a malignant primary liver carcinoma characterized by the unequivocal presence of both hepatocytic and cholangiocytic differentiation within the same tumor. Recent research has highlighted that cHCC-CCAs are more heterogeneous than previously expected. In the updated consensus terminology and WHO 2019 classification, “classical type” and “subtypes with stem-cell features” of the WHO 2010 classification are no longer recommended. Instead, it is recommended that the presence and percentages of various histopathologic components and stem-cell features be mentioned in the pathologic report. The new terminology and classification enable the exchange of clearer and more objective information about cHCC-CCAs, facilitating multi-center and multinational research. However, there are limitations to the diagnosis of cHCC-CCA by imaging and biopsy. cHCC-CCAs showing typical imaging findings of HCC could be misdiagnosed as HCC and subjected to inappropriate treatment, if other clinical findings are not sufficiently considered. cHCC-CCAs showing at least one of the CCA-like imaging features or unusual clinical features should be subjected to biopsy. There may be a sampling error for the biopsy diagnosis of cHCC-CCA. An optimized diagnostic algorithm integrating clinical, radiological, and histopathologic information of biopsy is required to resolve these diagnostic pitfalls.

Citations

Citations to this article as recorded by

Combined hepatocellular-cholangiocarcinoma: a contemporary pathologic and molecular perspective
Taek Chung
Journal of Liver Cancer.2026; 26(1): 1. CrossRef
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Jaeseung Shin, Taek Chung, Sang Yun Ha, Hyungjin Rhee
Journal of Liver Cancer.2026; 26(1): 9. CrossRef
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Rayane El Rahi, Murat Yüce, Bachir Taouli
Hematology/Oncology Clinics of North America.2026;[Epub] CrossRef
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Journal of Hepatology.2026;[Epub] CrossRef
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Bohyun Kim
Investigative Magnetic Resonance Imaging.2026; 30(2): 75. CrossRef
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Xinyao Liu, Lin Gong, Weiran Kong, Jie Kong, Yang Zhang, Chuantao Yuan, Shuai Chen
Biomarkers in Medicine.2026; : 1. CrossRef
Combined Hepatocellular-Cholangiocarcinoma: A Clinical and Molecular Review
Shaodian Xu, Julien Calderaro
Seminars in Liver Disease.2025; 45(04): 476. CrossRef
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Jeong-Ju Yoo, Sun Ah Maeng, Young Chang, Sae Hwan Lee, Soung Won Jeong, Jae Young Jang, Gab Jin Cheon, Young Seok Kim, Hong Soo Kim, Sang Gyune Kim
Scientific Reports.2024;[Epub] CrossRef
MRI features of combined hepatocellular-cholangiocarcinoma
Noor Fatima Majeed, Mathew Macey, Marta Braschi Amirfarzan, Sheida Sharifi, Jeremy R Wortman
Abdominal Radiology.2024; 50(1): 169. CrossRef
Imaging findings of intrahepatic cholangiocarcinoma for prognosis prediction and treatment decision-making: a narrative review
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The Ewha Medical Journal.2024;[Epub] CrossRef
Differentiation between hepatic angiomyolipoma and hepatocellular carcinoma in individuals who are not at-risk for hepatocellular carcinoma
Sungtae Park, Myeong-Jin Kim, Kyunghwa Han, Jae Hyon Park, Dai Hoon Han, Young Nyun Park, Jaehyo Kim, Hyungjin Rhee
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