• 대한의생명과학회지
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• 제28권4호
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• pp.260-275
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• 2022

Sterile alpha motif (SAM) domains bind to various proteins, lipids, and RNAs. However, these domains have not yet been analyzed as prognostic biomarkers. In this study, SAM domain containing 13 (SAMD13), a member of the SAM domain, was evaluated to identify a novel prognostic biomarker in various human cancers, including hepatocellular carcinoma (HCC). Moreover, we identified a correlation between SAMD13 expression and immune cell infiltration in HCC. We performed bioinformatics analysis using online databases, such as Tumor Immune Estimation Resource, UALCAN, Kaplan-Meier plotter, LinkedOmics, and Gene Expression Profiling Interactive Analysis2. SAMD13 expression in HCC samples was significantly higher than that in normal liver tissue; additionally, SAMD13 was higher in primary tumors, various stages of cancer and grades of tumor, and status of nodal metastasis. Higher SAMD13 expression was also associated with poorer prognosis. SAMD13 expression positively correlated with CD8+ T cells, CD4+ T cells, B cells, neutrophils, macrophages, and dendritic cells. In the analysis of SAMD13 co-expression networks, positively related genes of SAMD13 were associated with a high hazard ratio in different types of cancer, including HCC. In biological function of SAMD13, SAMD13 mainly include spliceosome, ribosome biogenesis in eukaryote, ribosome, etc. These results suggest that SAMD13 may serve as a novel prognostic biomarker for HCC diagnosis and provide novel insights into tumor immunology in HCC.

• Korean Journal of Radiology
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• 제22권3호
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• pp.354-365
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• 2021

Objective: To investigate the diagnostic performance of contrast-enhanced ultrasound (CEUS) and its role as a second-line imaging modality after gadoxetate-enhanced MRI (Gd-EOB-MRI) in the diagnosis of hepatocellular carcinoma (HCC) among at risk observations. Materials and Methods: We prospectively enrolled participants at risk of HCC with treatment-naïve solid hepatic observations (≥ 1 cm) of Liver Imaging Reporting and Data System (LR)-3/4/5/M during surveillance and performed Gd-EOB-MRI. A total of one hundred and three participants with 103 hepatic observations (mean size, 28.2 ± 24.5 mm; HCCs [n = 79], non-HCC malignancies [n = 15], benign [n = 9]; diagnosed by pathology [n = 57], or noninvasive method [n = 46]) were included in this study. The participants underwent CEUS with sulfur hexafluoride. Arterial phase hyperenhancement (APHE) and washout on Gd-EOB-MRI and CEUS were evaluated. The distinctive washout in CEUS was defined as mild washout 60 seconds after contrast injection. The diagnostic ability of Gd-EOB-MRI and of CEUS as a second-line modality for HCC were determined according to the European Association for the Study of the Liver (EASL) and the Korean Liver Cancer Association and National Cancer Center (KLCA-NCC) guidelines. The diagnostic abilities of both imaging modalities were compared using the McNemar's test. Results: The sensitivity of CEUS (60.8%) was lower than that of Gd-EOB-MRI (72.2%, p = 0.06 by EASL; 86.1%, p < 0.01 by KLCA-NCC); however, the specificity was 100%. By performing CEUS on the inconclusive observations in Gd-EOB-MRI, HCCs without APHE (n = 10) or washout (n = 12) on Gd-EOB-MRI further presented APHE (80.0%, 8/10) or distinctive washout (66.7%, 8/12) on CEUS, and more HCCs were diagnosed than with Gd-EOB-MRI alone (sensitivity: 72.2% vs. 83.5% by EASL, p < 0.01; 86.1% vs. 91.1% by KCLA-NCC, p = 0.04). There were no false-positive cases for HCC on CEUS. Conclusion: The addition of CEUS to Gd-EOB-MRI as a second-line diagnostic modality increases the frequency of HCC diagnosis without changing the specificities.

• Asian Pacific Journal of Cancer Prevention
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• 제17권7호
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• pp.3569-3573
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• 2016

Purpose: The aim of this study was to compare C-11 choline and F-18 FDG PET/CT, gadoxetic-enhanced 3-T MRI and contrast-enhanced CT for diagnosis of hepatocellular carcinoma (HCC). Materials and Methods: Twelve chronic hepatitis B patients suspected of having HCC by abdominal ultrasonography received all diagnostic modalities performed within a one-week timeslot. PET/CT results were analyzed visually by two independent nuclear medicine physicians and quantitatively by tumor to background ratio (T/B). Nine patients then had histopathological confirmation. Results: Six patients had well differentiated HCC, while two and one patient(s) were noted with moderately and poorly differentiated HCC, respectively. All were detected by both CT and MRI with an average tumor size of $5.7{\pm}3.8cm$. Five patients had positive C-11 choline and F-18 FDG uptake. Of the remaining four patients, three with well differentiated HCC showed negative F-FDG uptake (one of which showed negative results by both tracers) and one patient with moderately differentiated HCC demonstrated no C-11 choline uptake despite intense F-18 FDG avidity. The overall HCC detection rates with C-11 choline and F-18 FDG were 78% and 67%, respectively, while the sensitivity of F-18 FDG for non-well differentiated HCC was 100%, compared with 83% of C-11 choline. The average T/B of C-11 choline in well-differentiated HCC patients was higher than in moderately and poorly differentiated cases (p=0.5) and vice versa with statistical significance for T/B of F-18 FDG (p = 0.02). Conclusions: Our results suggested better detection rate in C-11 choline for well differentiated HCC than F-18 FDG PET. However, the overall detection rate of PET/CT with both tracers could not compare with contrast-enhanced CT and MRI.

• Korean Journal of Radiology
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• 제24권7호
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• pp.606-625
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• 2023

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.

• Asian Pacific Journal of Cancer Prevention
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• 제17권6호
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• pp.2857-2860
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• 2016

Background: Chronic hepatitis B (CHB) infection is one of the important causes of hepatocellular carcinoma (HCC) in Thailand, involved in the pathogenesis and leading to a development of HCC with or without cirrhotic changes of the liver. This study was aimed to investigate the predictive factors for HCC among CHB patients in a tertiary care center in Thailand. Materials and Methods: We conducted a retrospective study of CHB patients with or without HCC during the period of January 2009 and December 2014 at Thammasat University Hospital, Pathumthani, Thailand. Data on clinical characteristics, biochemical tests and radiologic findings were collected from review of medical records. Results: A total of 266 patients were diagnosed with CHB in Thammasat university hospital during the study period. However, clinical information of only 164/266 CHB patients (98 males, 66 females with mean age of 49.4 years) could be completely retrieved in this study. The prevalence of HCC in CHB infection in this study was 38/164 (23.2%). CHB patients with HCC had a mean age older than those without HCC (59.5 vs 47 years, P-value = 0.01). Furthermore, history of upper GI bleeding, tattooing, blood transfusion, and chronic alcoholism were significantly more common in CHB patients with HCC than patients without HCC (13.2% vs 3.2% P-value 0.03, OR = 4.6, 95%CI = 1.2-18.1, 20% vs 3.9%, P-value = 0.01, OR= 6.1, 95% CI= 1.6-23.6, 20% vs 6.3%, P-value = 0.03, OR = 3.8, 95%CI =1.1-12.7, 62.2% vs 30.3%, P-value <0.0001, OR = 3.7, 95%CI= 1.7-8.1 respectively). Interestingly, more CHB patients with HCC had evidence of cirrhosis than those without HCC (78.9% vs 20.4%, P-value <0.0001, OR = 14.6, 95%CI = 5.8-36.7). In CHB patients with HCC, surgical therapy provided longer survival than radiofrequency ablation (RFA) (72 vs 46.5 months, P-value= 0.04). The mean survival time after HCC diagnosis was 17.2 months. Conclusions: HCC remains a major problem among patients with CHB infection in Thailand. Possible risk factors are male gender, history of upper GI bleeding, chronic alcoholism, tattooing, blood transfusion and evidence of cirrhosis. For early stage HCC patients, surgical treatment provided longer survival time than RFA. Most HCC patients presented with advanced disease and had a grave prognosis. Appropriate screening of CHB patients at risk for HCC might be an appropriate approach for early detection and improvement of long-term outcomes.

• Asian Pacific Journal of Cancer Prevention
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• 제16권13호
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• pp.5181-5185
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• 2015

Background: CCAT1 has been reported to be linked with pathogenesis of malignancies including colon cancer and gastric cancer. However, the regulatory effect of CCAT1 in hepatocellular carcinoma (HCC) remains unclear. The purpose of this research was to identify any role of CCAT1 in the progression of HCC. Materials and Methods: Real time-PCR was performed to test the relative expression of CCAT1 in HCC tissues. A computation screen of CCAT1 promoter was conducted to search for transcription-factor-binding sites. The association of c-Myc with CCAT1 promoter in vivo was tested by Pearson correlation analysis and chromatin immunoprecipitation assay. Additionally, Kaplan-Meier analysis and Cox proportional hazards analyses were performed. Results: c-Myc directly binds to the E-box element in the promoter region of CCAT, and when ectopically expressed increases promoter activity and expression of CCAT1. Moreover, Kaplan-Meier analysis demonstrated that the patients with low expression of CCAT1 demonstrated better overall and relapse-free survival compared with the high expression group. Cox proportional hazards analyses showed that CCAT1 expression was an independent prognostic factor for HCC patients. Conclusions: The findings demonstrated CCAT1, acting as a potential biomarker in predicting the prognosis of HCC, is regulated by c-Myc.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6601-6604
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• 2013

Aim: Associations between polymorphisms in miR-146aG>C, miR-196a2C>T and miR-499A>G and risk of HCC, and interaction with HBV infection in a Chinese population, were the target of the present research. Methods: The duplex polymerase-chain-reaction with confronting-two-pair primers (PCR-RFLP) was performed to determine the genotypes of the miR-146aG>C, miR-196a2C>T and miR-499A>G genotypes. Associations of polymorphisms with the risk of HCC were estimated by conditional logistic regression analysis. Results: Drinking, family history of cancer, HBsAg and HCV were risk factors for HCC. Multivariate regression analyses showed that subjects carrying the miR-196a2 CC genotype had significantly increased risk of HCC, with an adjusted OR (95% CI) of 2.18 (1.23-3.80). In addition, cases carrying the miR-196a2 C allele had a 1.64-fold increase in the risk for HCC (95%CI=1.03-2.49). The miR-196a2 CT and TT genotypes greatly significantly increased the risk of HCC in subjects with HBV infection, with adjusted ORs (95% CI) of 2.02 (1.12-3.68) and 2.69 (1.28-5.71), respectively. Conclusion: Our results demonstrate that miR-196a2 CC genotype and C allele have an important role in HCC risk in Chinese, especially in patients with HBV infection.

• Molecules and Cells
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• 제45권12호
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• pp.935-949
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• 2022

Liver cancer has a high prevalence, with majority of the cases presenting as hepatocellular carcinoma (HCC). The prognosis of metastatic HCC has hardly improved over the past decade, highlighting the necessity for liver cancer research. Studies have reported the ability of the KiSS1 gene to inhibit the growth or metastasis of liver cancer, but contradictory research results are also emerging. We, therefore, sought to investigate the effects of KiSS1 on growth and migration in human HCC cells. HepG2 human HCC cells were infected with lentivirus particles containing KiSS1. The overexpression of KiSS1 resulted in an increased proliferation rate of HCC cells. Quantitative polymerase chain reaction and immunoblotting revealed increased Akt activity, and downregulation of the G1/S phase cell cycle inhibitors. A significant increase in tumor spheroid formation with upregulation of β-catenin and CD133 was also observed. KiSS1 overexpression promoted the migratory, invasive ability, and metastatic capacity of the hepatocarcinoma cell line, and these effects were associated with changes in the expressions of epithelial mesenchymal transition (EMT)- related genes such as E-cadherin, N-cadherin, and slug. KiSS1 overexpression also resulted in dramatically increased tumor growth in the xenograft mouse model, and upregulation of proliferating cell nuclear antigen (PCNA) and Ki-67 in the HCC tumors. Furthermore, KiSS1 increased the angiogenic capacity by upregulation of the vascular endothelial growth factor A (VEGF-A) and CD31. Based on these observations, we infer that KiSS1 not only induces HCC proliferation, but also increases the metastatic potential by increasing the migratory ability and angiogenic capacity.

• Asian Pacific Journal of Cancer Prevention
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• 제13권11호
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• pp.5433-5438
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• 2012

Background: Hepatocellular carcinoma (HCC) is a common and aggressive malignancy. Despite of the improvements in its treatment, HCC prognosis remains poor due to its recurrence after resection. This study provides complete genetic profile for Egyptian HCC. Genome-wide analyses were performed to identify the predictive signatures. Patients and Methods: Liver tissue was collected from 31 patients with diagnosis of HCC and gene expression levels in the tumours and their adjacent non-neoplastic tissues samples were studied by analyzing changes by microarray then correlate these with the clinico-pathological parameters. Genes were validated in an independent set by qPCR. The genomic profile was associated with genetic disorders and cancer focused on gene expression, cell cycle and cell death. Molecular profile analysis revealed cell cycle progression and arrest at G2/M, but progression to mitosis; unregulated DNA damage check-points, and apoptosis. Result: Nine hundred fifty eight transcripts out of the 25,000 studied cDNAs were differentially expressed; 503 were up-regulated and 455 were down-regulated. A total of 19 pathways were up-regulated through 27 genes and 13 pathways were down-regulated through 19 genes. Thirty-seven genes showed significant differences in their expression between HCC cases with high and low Alpha Feto Protein ($AFP{\geq}600$ IU/ml). The validation for the microarray was done by real time PCR assay in which PPP3CA, ATG-5, BACE genes showed down-regulation and ABCG2, RXRA, ELOVL2, CXR3 genes showed up-regulation. cDNA microarrays showed that among the major upregulated genes in HCC are sets. Conclusion: The identified genes could provide a panel of new diagnostic and prognostic aids for HCC.

• Radiation Oncology Journal
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• 제35권2호
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• pp.185-188
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• 2017

Primary liver tumor, especially hepatocellular carcinoma (HCC), is a common cause of cancer death worldwide. The incidence is generally higher in Asian countries than in western countries. Carcinogenesis of HCC is often associated with hepatitis viral infections. Current standard treatment of HCC is surgical resection or transplantation in patients with early stage disease. However, the patient with advanced stage disease, surgical resection is often limited. Sorafenib or other treatment modalities are not so effective as well. We report a case of unusual radiation super-sensitivity in advanced stage HCC, and review the literature.