Journal of Liver Cancer

Review Articles

Advancing Korean nationwide registry for hepatocellular carcinoma: a systematic sampling approach utilizing the Korea Central Cancer Registry database: Bo Hyun Kim, E Hwa Yun, Jeong-Hoon Lee, Geun Hong, Jun Yong Park, Ju Hyun Shim, Eunyang Kim, Hyun-Joo Kong, Kyu-Won Jung, Young-Suk Lim; J Liver Cancer. 2024;24(1):57-61. Published online March 26, 2024; DOI: https://doi.org/10.17998/jlc.2024.03.03

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Abstract PDF Supplementary Material: Hepatocellular carcinoma (HCC) presents a substantial public health challenge in South Korea as evidenced by 10,565 new cases annually (incidence rate of 30 per 100,000 individuals), in 2020. Cancer registries play a crucial role in gathering data on incidence, disease attributes, etiology, treatment modalities, outcomes, and informing health policies. The effectiveness of a registry depends on the completeness and accuracy of data. Established in 1999 by the Ministry of Health and Welfare, the Korea Central Cancer Registry (KCCR) is a comprehensive, legally mandated, nationwide registry that captures nearly all incidence and survival data for major cancers, including HCC, in Korea. However, detailed information on cancer staging, specific characteristics, and treatments is lacking. To address this gap, the KCCR, in partnership with the Korean Liver Cancer Association (KLCA), has implemented a systematic approach to collect detailed data on HCC since 2010. This involved random sampling of 10-15% of all new HCC cases diagnosed since 2003. The registry process encompassed four stages: random case selection, meticulous data extraction by trained personnel, expert validation, anonymization of personal data, and data dissemination for research purposes. This random sampling strategy mitigates the biases associated with voluntary reporting and aligns with stringent privacy regulations. This innovative approach positions the KCCR and KLCA as foundations for advancing cancer control and shaping health policies in South Korea.

Changing etiology and epidemiology of hepatocellular carcinoma: Asia and worldwide: Do Young Kim; J Liver Cancer. 2024;24(1):62-70. Published online March 25, 2024; DOI: https://doi.org/10.17998/jlc.2024.03.13

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Abstract PDF: Approximately 80% of hepatocellular carcinoma (HCC) cases arise in sub-Saharan Africa and Eastern Asia, following a similarly high prevalence of chronic hepatitis B virus (HBV) carriers in these regions. The etiology and epidemiology of HCC have recently changed worldwide. Although HBV infection is the main contributor to HCC development, a slow but continuous decline in HBV infection rates has been reported since 1990. Owing to the widespread use of direct-acting antivirals, the incidence of hepatitis C virus-related HCC has remarkably decreased in Japan and European countries. In Korea, Taiwan, and Singapore, the incidence of HBV-related HCC has significantly decreased owing to vaccination against HBV. Globally, while HBV accounted for more than half of HCCs in 1990, this had decreased to 42% in 2019. In contrast, the proportion of patients with alcoholic- and nonalcoholic steatohepatitis (NASH) increased from 13% to 18% and from 5% to 6%, respectively. NASH-related HCC has characteristics that differ from those of virus-associated HCC. Compared with other etiologies, patients with NASHassociated HCC are older, have a higher body mass index, and have higher rates of type 2 diabetes mellitus, hypertension, hyperlipidemia, and cardiovascular disease. Nonalcoholic fatty liver disease (NAFLD)-associated HCC is also known to develop in the absence of cirrhosis, unlike alcohol-related and autoimmune liver diseases. Because patients with NAFLD usually have diabetes or obesity, surveying this population is challenging. Optimal selection of the target population and surveillance tools among patients with NAFLD needs to be determined.

Multidisciplinary approach for hepatocellular carcinoma patients: current evidence and future perspectives: Joo Hyun Oh, Dong Hyun Sinn; J Liver Cancer. 2024;24(1):47-56. Published online March 25, 2024; DOI: https://doi.org/10.17998/jlc.2024.02.27

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Abstract PDF: Management of hepatocellular carcinoma (HCC) is challenging due to the complex relationship between underlying liver disease, tumor burden, and liver function. HCC is also notorious for its high recurrence rate even after curative treatment for early-stage tumor. Liver transplantation can substantially alter patient prognosis, but donor availability varies by each patient which further complicates treatment decision. Recent advancements in HCC treatments have introduced numerous potentially efficacious treatment modalities. However, high level evidence comparing the risks and benefits of these options is limited. In this complex situation, multidisciplinary approach or multidisciplinary team care has been suggested as a valuable strategy to help cope with escalating complexity in HCC management. Multidisciplinary approach involves collaboration among medical and health care professionals from various academic disciplines to provide comprehensive care. Although evidence suggests that multidisciplinary care can enhance outcomes of HCC patients, robust data from randomized controlled trials are currently lacking. Moreover, the implementation of a multidisciplinary approach necessitates increased medical resources compared to conventional cancer care. This review summarizes the current evidence on the role of multidisciplinary approach in HCC management and explores potential future directions.

Current perspectives on radiotherapy in hepatocellular carcinoma management: a comprehensive review: Dowook Kim, Jun-Sang Kim; J Liver Cancer. 2024;24(1):33-46. Published online March 25, 2024; DOI: https://doi.org/10.17998/jlc.2024.02.26

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Abstract PDF: This review examines the transformative role of external beam radiotherapy (EBRT) in managing hepatocellular carcinoma (HCC), spotlighting the progression from traditional EBRT techniques to advanced modalities like intensity-modulated radiotherapy (RT), stereotactic body RT (SBRT), and innovative particle therapy, including proton beam therapy and carbon ion RT. These advancements have significantly improved the precision and efficacy of RT, marking a paradigm shift in the multimodal management of HCC, particularly in addressing complex cases and enhancing local tumor control. The review underscores the synergistic potential of integrating RT with other treatments like transarterial chemoembolization, systemic therapies such as sorafenib, and emerging immunotherapies, illustrating enhanced survival and disease control outcomes. The efficacy of RT is addressed for challenging conditions, including advanced HCC with macrovascular invasion, and RT modalities, like SBRT, are compared against traditional treatments like radiofrequency ablation for early-stage HCC. Additionally, the review accentuates the encouraging outcomes of particle therapy in enhancing local control and survival rates, minimizing treatment-related toxicity, and advocating for continued research and clinical trials. In conclusion, the integration of RT into multimodal HCC treatment strategies, coupled with the emergence of particle therapy, is crucial for advancing oncologic management, emphasizing the need for relentless innovation and personalized treatment approaches.

Intermediate-stage hepatocellular carcinoma: refining substaging or shifting paradigm?: Bernardo Stefanini, Luca Ielasi, Dante Pio Pallotta, Sofia Penazza, Mariarosaria Marseglia, Fabio Piscaglia; J Liver Cancer. 2024;24(1):23-32. Published online March 12, 2024; DOI: https://doi.org/10.17998/jlc.2024.02.21

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Abstract PDF: This review explores the evolution of cancer staging, focusing on intermediate hepatocellular carcinoma (HCC), and the challenges faced by physicians. The Barcelona Clinic Liver Cancer (BCLC) staging system, introduced in 1999, was designed to address the limitations associated with providing accurate prognostic information for HCC and allocating specific treatments, to avoid overtreatment. However, criticism has emerged, particularly regarding the intermediate stage of HCC (BCLC-B) and its heterogeneous patient population. To overcome this limitation, various subclassification systems, such as the Bolondi and Kinki criteria, have been proposed. These systems are aimed at refining categorizations within the intermediate stage and have demonstrated varying degrees of success in predicting outcomes through external validation. This study discusses the shift in treatment paradigms, emphasizing the need for a more personalized approach rather than strictly adhering to cancer stages, without dismissing the relevance of staging systems. It assesses the available treatment options for intermediate-stage HCC, highlighting the importance of considering surgical and nonsurgical options alongside transarterial chemoembolization for optimal outcomes. In conclusion, the text advocates for a paradigm shift in staging systems prioritizing treatment suitability over cancer stage. This reflects the evolving landscape of HCC management, where a multidisciplinary approach is crucial for tailoring treatments to individual patients, ultimately aiming to improve overall survival.

Complications of immunotherapy in advanced hepatocellular carcinoma: Young-Gi Song, Jeong-Ju Yoo, Sang Gyune Kim, Young Seok Kim; J Liver Cancer. 2024;24(1):9-16. Published online November 29, 2023; DOI: https://doi.org/10.17998/jlc.2023.11.21

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Abstract PDF: Immune checkpoint inhibitors (ICIs) are highly effective in cancer treatment. However, the risks associated with the treatment must be carefully balanced against the therapeutic benefits. Immune-related adverse events (irAEs) are generally unpredictable and may persist over an extended period. In this review, we analyzed common irAEs reported in highly cited original articles and systematic reviews. The prevalent adverse reactions include fatigue, pyrexia, rash, pruritus, diarrhea, decreased appetite, nausea, abdominal pain, constipation, hepatitis, and hypothyroidism. Therefore, it is crucial to conduct evaluations not only of gastrointestinal organs but also of cardiac, neurologic, endocrine (including the frequently affected thyroid), and ophthalmic systems before commencing ICIs. This review further explores commonly reported types of irAEs, specific irAEs associated with each ICI agent, rare yet potentially fatal irAEs, and available treatment options for managing them.

A multidisciplinary approach with immunotherapies for advanced hepatocellular carcinoma: Yu Rim Lee; J Liver Cancer. 2023;23(2):316-329. Published online September 22, 2023; DOI: https://doi.org/10.17998/jlc.2023.09.04

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2 Citations

Abstract PDF

Hepatocellular carcinoma (HCC) is a highly aggressive disease that is usually diagnosed at an advanced stage. Advanced HCC has limited treatment options and often has a poor prognosis. For the past decade, tyrosine kinase inhibitors have been the only treatments approved for advanced HCC that have shown overall survival (OS) benefits; however, but their clinical efficacy has been limited. Recent trials have demonstrated promising advancements in survival outcomes through immunotherapy-based treatments, such as combinations of immune checkpoint inhibitors (ICIs) with other ICIs, antiangiogenic drugs, and locoregional therapies. The atezolizumab-bevacizumab and durvalumab-tremelimumab (STRIDE) regimen has significantly improved survival rates as a first-line treatment and has become the new standard of care. Therefore, combined treatments for advanced HCC can result in better treatment outcomes owing to their synergistic effects, which requires a multidisciplinary approach. Ongoing studies are examining other therapeutic innovations that can improve disease control and OS rates. Despite improvements in the treatment of advanced HCC, further studies on the optimal treatment selection and sequences, biomarker identification, combination approaches with other therapies, and development of novel immunotherapy agents are required. This review presents the current treatment options and clinical data of the ICI-based combination immunotherapies for advanced HCC from a multidisciplinary perspective.

Citations

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Reduced-Dose or Discontinuation of Bevacizumab Might Be Considered after Variceal Bleeding in Patients with Hepatocellular Carcinoma Receiving Atezolizumab/Bevacizumab: Case Reports
Kyeong-Min Yeom, Young-Gi Song, Jeong-Ju Yoo, Sang Gyune Kim, Young Seok Kim
Medicina.2024; 60(1): 157. CrossRef
Hepatocellular Carcinoma: Advances in Systemic Therapy
Insija Ilyas Selene, Merve Ozen, Reema A. Patel
Seminars in Interventional Radiology.2024; 41(01): 056. CrossRef

Management of early-stage hepatocellular carcinoma: challenges and strategies for optimal outcomes: Jae Hyun Yoon, Sung Kyu Choi; J Liver Cancer. 2023;23(2):300-315. Published online September 21, 2023; DOI: https://doi.org/10.17998/jlc.2023.08.27

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144 Downloads
4 Citations

Abstract PDF

Although hepatocellular carcinoma (HCC) is associated with a poor prognosis, management of early-stage HCC is often successful with highly efficacious treatment modalities such as liver transplantation, surgical resection, and radiofrequency ablation. However, unfavorable clinical outcomes have been observed under certain circumstances, even after efficient treatment. Factors that predict unsuitable results after treatment include tumor markers, inflammatory markers, imaging findings reflecting tumor biology, specific outcome indicators for each treatment modality, liver functional reserve, and the technical feasibility of the treatment modalities. Various strategies may overcome these challenges, including the application of reinforced treatment indication criteria with predictive markers reflecting tumor biology, compensation for technical issues with up-to-date technologies, modification of treatment modalities, downstaging with locoregional therapies (such as transarterial chemotherapy or radiotherapy), and recently introduced combination immunotherapies. In this review, we discuss the challenges to achieving optimal outcomes in the management of early-stage HCC and suggest strategies to overcome these obstacles.

Citations

Citations to this article as recorded by

Diosgenin potentiates the anticancer effect of doxorubicin and volasertib via regulating polo-like kinase 1 and triggering apoptosis in hepatocellular carcinoma cells
Eman H. Yousef, Mohamed E. El-Mesery, Maha R. Habeeb, Laila A. Eissa
Naunyn-Schmiedeberg's Archives of Pharmacology.2024;[Epub] CrossRef
Comparison of Surgical Resection and Radiofrequency Ablation in Elderly Patients with Hepatocellular Carcinoma
Jun Il Kim, Jayoun Lee, Gi Hong Choi, Min Woo Lee, Dong Ah Park, Jeong-Ju Yoo
Digestive Diseases and Sciences.2024; 69(3): 1055. CrossRef
Radiofrequency for hepatocellular carcinoma larger than 3 cm: potential for applications in daily practice
Ji Hoon Kim, Pil Soo Sung
Journal of Liver Cancer.2024; 24(1): 1. CrossRef
Efficacy of Transarterial Chemoembolization (TACE) for Early-Stage Hepatocellular Carcinoma
Moonhyung Lee, Hyun Phil Shin
Medicina.2023; 59(12): 2174. CrossRef

Diagnosis of hepatocellular carcinoma using Sonazoid: a comprehensive review: Woo Kyoung Jeong; J Liver Cancer. 2023;23(2):272-283. Published online September 19, 2023; DOI: https://doi.org/10.17998/jlc.2023.08.25

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1 Citation

Abstract PDF

Sonazoid contrast-enhanced ultrasonography (CEUS) is a promising technique for the detection and diagnosis of focal liver lesions, particularly hepatocellular carcinoma (HCC). Recently, a collaborative effort between the Korean Society of Radiology and Korean Society of Abdominal Radiology resulted in the publication of guidelines for diagnosing HCC using Sonazoid CEUS. These guidelines propose specific criteria for identifying HCC based on the imaging characteristics observed during Sonazoid CEUS. The suggested diagnostic criteria include nonrim arterial phase hyperenhancement, and the presence of late and mild washout, or Kupffer phase washout under the premise that the early or marked washout should not occur during the portal venous phase. These criteria aim to improve the accuracy of HCC diagnosis using Sonazoid CEUS. This review offers a comprehensive overview of Sonazoid CEUS in the context of HCC diagnosis. It covers the fundamental principles of Sonazoid CEUS and its clinical applications, and introduces the recently published guidelines. By providing a summary of this emerging technique, this review contributes to a better understanding of the potential role of Sonazoid CEUS for diagnosing HCC.

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Sonazoid contrast-enhanced ultrasonography for the diagnosis of hepatocellular carcinoma: strengths and shortcomings
Sung Won Lee, Min Kyu Kang, Xiang Zhang
Journal of Liver Cancer.2023; 23(2): 238. CrossRef

Imaging prognostication and tumor biology in hepatocellular carcinoma: Diana Kadi, Marilyn F. Yamamoto, Emily C. Lerner, Hanyu Jiang, Kathryn J. Fowler, Mustafa R. Bashir; J Liver Cancer. 2023;23(2):284-299. Published online September 15, 2023; DOI: https://doi.org/10.17998/jlc.2023.08.29

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Abstract PDF: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, and represents a significant global health burden with rising incidence rates, despite a more thorough understanding of the etiology and biology of HCC, as well as advancements in diagnosis and treatment modalities. According to emerging evidence, imaging features related to tumor aggressiveness can offer relevant prognostic information, hence validation of imaging prognostic features may allow for better noninvasive outcomes prediction and inform the selection of tailored therapies, ultimately improving survival outcomes for patients with HCC.

Original Articles

Clinical outcome of surgical resection for multifocal T2-T3 hepatocellular carcinoma up to 3 nodules: a comparative analysis with a single nodule: Sehyeon Yu, Hye-Sung Jo, Young-Dong Yu, Yoo jin Choi, Dong-Sik Kim; J Liver Cancer. 2023;23(2):377-388. Published online September 15, 2023; DOI: https://doi.org/10.17998/jlc.2023.08.24

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Abstract PDF Supplementary Material: Background/Aim
s: Although the Barcelona Clinic Liver Cancer staging system seems to underestimate the impact of curative-intent surgical resection for multifocal hepatocellular carcinoma (HCC), recent studies have indicated favorable results for the surgical resection of multiple HCC. This study aimed to assess clinical outcomes and feasibility of surgical resection for multifocal HCC with up to three nodules compared with single tumor cases.
Methods
Patients who underwent surgical resection for HCC with up to three nodules between 2009 and 2020 were included, and those with the American Joint Committee on Cancer (AJCC) 8th edition, T1 and T4 stages were excluded to reduce differences in disease distribution and severity. Finally, 81 and 52 patients were included in the single and multiple treatment groups, respectively. Short- and long-term outcomes including recurrence-free survival (RFS) and overall survival (OS), were evaluated.
Results
All patients were classified as Child-Pugh class A. RFS and OS were not significantly different between the two groups (P=0.176 and P=0.966, respectively). Multivariate analysis revealed that transfusion and intrahepatic metastasis were significantly associated with recurrence (P=0.046 and P=0.005, respectively). Additionally, intrahepatic metastasis was significantly associated with OS (hazard ratio, 1.989; 95% confidence interval, 1.040-3.802; P=0.038).
Conclusions
Since there was no significant difference in survival between the single and multiple groups among patients with AJCC 8th stage T2 and T3, surgical resection with curative intent could be considered with acceptable long-term survival for selected patients with multiple HCC of up to three nodules.

Nomogram for predicting overall survival in patients with large (>5 cm) hepatocellular carcinoma based on real-world practice: Nalee Kim, Jeong Il Yu, Hee Chul Park, Jung Yong Hong, Ho Yeong Lim, Myung Ji Goh, Yong-Han Paik; J Liver Cancer. 2023;23(2):350-361. Published online September 6, 2023; DOI: https://doi.org/10.17998/jlc.2023.08.10

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Abstract PDF Supplementary Material: Background/Aim
Patients with large (>5 cm) hepatocellular carcinoma (HCC) have limited treatment options, thus necessitating the identification of prognostic factors and the development of predictive tools. This study aimed to identify prognostic factors and to construct a nomogram to predict survival outcomes in patients with large HCC.
Methods
A cohort of 438 patients, who were diagnosed with large HCC at a tertiary hospital between 2015 and 2018, was analyzed. Cox proportional hazards models were used to identify key prognosticators of overall survival (OS), and an independent set of prognostic factors was used to develop a nomogram. The discrimination and calibration abilities of the nomogram were assessed and internal validation was performed using cross-validation and bootstrapping methods.
Results
During a median follow-up of 9.3 months, the median OS was 9.9 months, and the 1-year OS rate was 43.9%. Multivariable Cox regression analysis revealed that performance status, modified albumin-bilirubin grade, tumor size, extent of portal vein tumor thrombosis, and initial treatment significantly affected OS. The newly developed nomogram incorporating these variables demonstrated favorable accuracy (Harrell’s concordance index, 0.807).
Conclusions
The newly developed nomogram facilitated the estimation of individual survival outcomes in patients with large HCC, providing an acceptable level of accuracy.

Review Article

The role of lenvatinib in the era of immunotherapy of hepatocellular carcinoma: Matthew Man Pok Lee, Landon Long Chan, Stephen Lam Chan; J Liver Cancer. 2023;23(2):262-271. Published online August 17, 2023; DOI: https://doi.org/10.17998/jlc.2023.07.17

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253 Downloads
2 Citations

Abstract PDF

Hepatocellular carcinoma (HCC) frequently presents as advanced stage with poor prognosis and high mortality. Systemic treatment is the treatment of choice for advanced disease. In 2007, the first multi-kinase inhibitor (MKI) sorafenib was approved and shown to modestly prolong overall survival (OS). The progress of systemic therapy has been slow afterwards until 2018 when lenvatinib, another MKI, was shown to be non-inferior to sorafenib on median OS as the first-line therapy for HCC. Since then, remarkable progress has been achieved on the treatment of advanced HCC, including the development of second-line targeted treatment, including regorafenib, cabozantinib and ramucirumab from 2017 to 2019. A growing focus has been placed on immune checkpoint inhibitors (ICIs) targeting programmed cell death-1 (PD-1), its ligand PD-L1, and cytotoxic T-lymphocyte-associated protein 4. These ICIs have proven their potency in treating HCC as both initial and subsequent line of therapy. At present, both regimens of atezolizumab combined with bevacizumab, as well as the combination of tremelimumab and durvalumab, are recommended as the first-line treatments based on positive phase III clinical trials. With the advancement of ICIs, it is anticipated that the role of MKIs in the treatment of HCC will evolve. In this article, lenvatinib, one of the most commonly used MKIs in HCC, is chosen to be reviewed.

Citations

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Reduced-Dose or Discontinuation of Bevacizumab Might Be Considered after Variceal Bleeding in Patients with Hepatocellular Carcinoma Receiving Atezolizumab/Bevacizumab: Case Reports
Kyeong-Min Yeom, Young-Gi Song, Jeong-Ju Yoo, Sang Gyune Kim, Young Seok Kim
Medicina.2024; 60(1): 157. CrossRef
The Position of Multikinase Inhibitors in the Era of Immune-Checkpoint Inhibitors for Hepatocellular Carcinoma
Beom Kyung Kim
Gut and Liver.2024; 18(1): 3. CrossRef

Recommendation and Guideline

Transarterial chemoembolization for hepatocellular carcinoma: 2023 expert consensus-based practical recommendations of the Korean Liver Cancer Association: Yuri Cho, Jin Woo Choi, Hoon Kwon, Kun Yung Kim, Byung Chan Lee, Hee Ho Chu, Dong Hyeon Lee, Han Ah Lee, Gyoung Min Kim, Jung Suk Oh, Dongho Hyun, In Joon Lee, Hyunchul Rhim; J Liver Cancer. 2023;23(2):241-261. Published online July 14, 2023; DOI: https://doi.org/10.17998/jlc.2023.05.22

2,213 Views
139 Downloads
3 Citations

Abstract PDF

Transarterial chemoembolization (TACE) was introduced in 1977 with the administration of chemotherapeutic agent to gelatin sponge particles through the hepatic artery in patients with hepatocellular carcinoma (HCC) and was established as conventional TACE using Lipiodol in the 1980s. In the 2000s, drug-eluting beads were developed and applied clinically. Currently, TACE is a commonly used non-surgical treatment modality for patients with HCC who are unsuitable for curative treatment. Considering the vital role of TACE in the management of HCC, it is crucial to organize current knowledge and expert opinions regarding patient preparation, procedural techniques, and post-treatment care in TACE, which can enhance therapeutic efficacy and safety. A group of 12 experts in the fields of interventional radiology and hepatology, convened by the Research Committee of the Korean Liver Cancer Association (KLCA), has developed expert consensus-based practical recommendations in TACE. These recommendations have been endorsed by the Korean Society of Interventional Radiology and provide useful information and direction in performing TACE procedure as well as pre- and post- procedural patient care.

Citations

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Liver resection in selective hepatocellular carcinoma with Vp3 or Vp4 portal vein tumor thrombosis improves prognosis
Manuel Lim, Jongman Kim, Jinsoo Rhu, Gyu-Seong Choi, Jae-Won Joh
Journal of Liver Cancer.2024; 24(1): 102. CrossRef
A refined prediction model for survival in hepatocellular carcinoma patients treated with transarterial chemoembolization
Hae Lim Lee, Seok Hwan Kim, Hee Yeon Kim, Sung Won Lee, Myeong Jun Song
Frontiers in Oncology.2024;[Epub] CrossRef
Implications of the first edition of the Korean expert consensus-based practice recommendations for transarterial chemoembolization in the management of hepatocellular carcinoma
Jin Wook Chung
Journal of Liver Cancer.2023; 23(2): 235. CrossRef

Original Article

Isolation and characterization of cancer-associated fibroblasts in the tumor microenvironment of hepatocellular carcinoma: Kyoungdo Mun, Jiwon Han, Pureun Roh, Jonggeun Park, Gahee Kim, Wonhee Hur, Jeongwon Jang, Jongyoung Choi, Seungkew Yoon, Youngkyoung You, Hojoong Choi, Pilsoo Sung; J Liver Cancer. 2023;23(2):341-349. Published online June 12, 2023; DOI: https://doi.org/10.17998/jlc.2023.04.30

2,508 Views
167 Downloads
1 Citation

Abstract PDF

Background/Aim
Cancer-associated fibroblasts (CAFs) play an immunosuppressive role in the tumor microenvironment (TME) of human cancers; however, their characteristics and role in hepatocellular carcinoma (HCC) remain to be elucidated.
Methods
Nine tumor and surrounding liver tissue samples from patients with HCC who underwent surgery were used to isolate patient-derived CAFs. Cell morphology was observed using an optical microscope after culture, and cell phenotypes were evaluated using flow cytometry and immunoblotting. Cytokines secreted by CAFs into culture medium were quantified using a multiplex cytokine assay.
Results
CAFs were abundant in the TME of HCC and were adjacent to immune cells. After culture, the CAFs and non-tumor fibroblasts exhibited spindle shapes. We observed a robust expression of alpha-smooth muscle actin and fibroblast activation protein in CAFs, whereas alpha-fetoprotein, epithelial cell adhesion molecule, platelet/endothelial cell adhesion molecule-1, and E-cadherin were not expressed in CAFs. Furthermore, CAFs showed high secretion of various cytokines, namely C-X-C motif chemokine ligand 12, interleukin (IL)-6, IL-8, and C-C motif chemokine ligand 2.
Conclusions
CAFs are abundant in the TME of HCC and play a crucial role in tumor progression. These fibroblasts secrete cytokines that promote tumor growth and metastasis.

Citations

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Rebuilding the microenvironment of primary tumors in humans: a focus on stroma
Siwon Mun, Hyun Jin Lee, Pilnam Kim
Experimental & Molecular Medicine.2024; 56(3): 527. CrossRef

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