• Genomics & Informatics
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• v.7 no.4
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• pp.187-194
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• 2009

Cytochrome P450 2E1 (CYP2E1) is a member of the cytochrome P450 superfamily, and it is a key enzyme responsible for the metabolic activation of many smallmolecular-weight compounds such as alcohol, which is classified as a human carcinogen. In this study, we identified 19 single nucleotide polymorphisms (SNPs) in CYP2E1 in Korean population. In these SNPs, we examined possible genetic association of CYP2E1 polymorphisms with HBV clearance and the risk of hepatocellular carcinoma (HCC). Five common polymorphic sites were selected, CYP2E1 polymorphisms at rs381-3867, rs3813870, rs2070673, rs2515641 and rs2480257, considering their allele frequencies, haplotype-tagging status and LDs for genotyping in larger-scale subjects (n=1,092). Statistical analysis demonstrated that CYP2E1 polymorphisms and haplotypes show no significant association with HBV clearance, HCC occurrence and onset age of HCC (p>0.05). Previous studies, however, have shown contradictory findings on associations of CYP2E1 polymorphisms with CYP2E1 activities and HCC risk. Comparing the contrasting results of previous researches suggest that CYP2E1 polymorphism is associated with CYP2E1 activity induced by ethanol, but is not directly associated with HCC risk. CYP2E1 variation/haploype information identified in this study will provide valuable information for future studies on CYP2E1.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.2033-2036
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• 2013

Many studies have suggested that the XRCC1 Arg280His gene polymorphism might be involved in the development of hepatocellular carcinoma (HCC). However, the results have been inconsistent. In this study, the authors performed a meta-analysis to assess the association between XRCC1 Arg280His and HCC susceptibility. Published literature from PubMed, EMBASE and CNKI Data was searched. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using fixed- or random-effects models when appropriate. Begg's test was used to measure publication bias. A total of 7 case-control studies covering 1,448 HCC cases and 1,544 controls were included. No significant variation in HCC risk was detected in any of the genetic models overall. In the stratified analysis, four studies with sample sizes over 300 produced similar results. The corresponding pooled ORs were not substantially altered after the exclusion of three studies deviating from Hardy-Weinberg equilibrium in the control group, which indicated reliability for our meta-analysis results.

• IMMUNE NETWORK
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• v.20 no.1
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• pp.11.1-11.14
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• 2020

Most patients with hepatocellular carcinoma (HCC) are diagnosed at an advanced stage of disease. Until recently, systemic treatment options that showed survival benefits in HCC have been limited to tyrosine kinase inhibitors, antibodies targeting oncogenic signaling pathways or VEGF receptors. The HCC tumor microenvironment is characterized by a dysfunction of the immune system through multiple mechanisms, including accumulation of various immunosuppressive factors, recruitment of regulatory T cells and myeloid-derived suppressor cells, and induction of T cell exhaustion accompanied with the interaction between immune checkpoint ligands and receptors. Immune checkpoint inhibitors (ICIs) have been interfered this interaction and have altered therapeutic landscape of multiple cancer types including HCC. In this review, we discuss the use of anti-PD-1, anti-PD-L1, and anti-CTLA-4 antibodies in the treatment of advanced HCC. However, ICIs as a single agent do not benefit a significant portion of patients. Therefore, various clinical trials are exploring possible synergistic effects of combinations of different ICIs (anti-PD-1/PD-L1 and anti-CTLA-4 antibodies) or ICIs and target agents. Combinations of ICIs with locoregional therapies may also improve therapeutic responses.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.1
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• pp.439-443
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• 2016

Background: To assess the effect of an information leaflet on the level of Chinese youth's knowledge about hepatitis B and hepatocellular carcinoma (HCC), the most common type of primary liver cancer (PLC). Materials and Methods: A total of 500 students, from two universities in the Chaoshan area of China, were randomly divided into an intervention group of 280 participants and a control group of 220. Baseline knowledge of HCC and hepatitis B was evaluated by questionnaire interview. Subsequently, only the intervention group was given an information leaflet of HCC and hepatitis B. Three months later, the two groups were contacted for a second interview. Changes in knowledge from baseline of HCC and hepatitis B were compared between the two groups. Results: There was no statistically significant difference in mean PRE-questionnaire scores between the intervention and control groups. However, the mean POST-questionnaire score was significantly higher in the intervention group after the intervention. The leaflet had the greatest effect on the participants' questionnaire score, and raised their level of knowledge about HCC and hepatitis B. Conclusions: The information leaflet intervention is significantly effective in improving the knowledge of HCC and hepatitis B among the youth.

• BMB Reports
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• v.51 no.12
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• pp.630-635
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• 2018

C-X-C motif chemokine ligand 2 (CXCL2) is a small secreted protein that exhibits a structure similar to the proangiogenic subgroup of the CXC chemokine family. Recently, accumulating evidence suggests that chemokines play a pivotal role in cancer progression and carcinogenesis. We examined the expression levels of 7 types of $ELR^+$ CXCLs messenger RNA (mRNA) in 264 clinical samples. We found that CXCL2 expression was stably down-regulated in 94% of hepatocellular carcinoma (HCC) specimens compared with paired adjacent normal liver tissues and some HCC cell lines. Moreover, CXCL2 overexpression profoundly attenuated HCC cell proliferation and growth and induced apoptosis in vitro. In animal studies, we found that overexpressing CXCL2 by lentivirus also apparently inhibited the size and weight of subcutaneous tumours in nude mice. Furthermore, we demonstrated that CXCL2 induced HCC cell apoptosis via both nuclear and mitochondrial apoptosis pathways. Our results indicate that CXCL2 negatively regulates the cell cycle in HCC cells via the ERK1/2 signalling pathway. These results provide new insights into HCC and may ultimately lead to the discovery of innovative therapeutic approaches of HCC.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6955-6959
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• 2013

The incidence of hepatocellular carcinoma (HCC) is relatively high in Southeast Asia. Globally, HCC has a high fatality rate and short survival. The objectives of this retrospective cohort study were to review the epidemiology and survival of HCC patients at a tertiary centre in north-east of Peninsular Malaysia. Subjects were adult HCC patients diagnosed by histopathology or radio-imaging. Secondary liver carcinoma was excluded. Kaplan Meier and multiple Cox proportional hazard survival analyses were used. Only 210 HCC cases from years 1987-2008, were included in the final analysis. The number of cases was increasing annually. The mean age was 55.0 (SD 13.9) years with male:female ratio of 3.7:1. Approximately 57.6% had positive hepatitis B virus, 2.4% hepatitis C virus, 20% liver cirrhosis and 8.1% chronic liver disease. Only 2.9% had family history and 9.0% had frequently consumed alcohol. Most patients presented with abdominal pain or discomfort and had hepatomegaly, 47.9% had an elevated ${\alpha}$-fetoprotein level of 800 IU/ml or more, 51.9% had multiple tumors and 44.8% involved multiple liver lobes. Approximately 63.3% were in stage 3 and 23.4% in stage 4, and 82.9% did not receive any treatment. The overall median survival time was 1.9 months (95% confidence interval (CI): 1.5, 2.3). The 1-month, 6-month, 1-year and 2-year survival rates were 71.8%, 23.3%, 13.0% and 7.3% respectively. Significant prognostic factors were Malay ethnicity [Adjusted hazard ratio (AHR) 1.6; 95%CI: 1.0, 2.5; p=0.030], no chemotherapy [AHR 1.7; 95%CI: 1.1, 2.5; p=0.017] and Child-Pugh class C [AHR 2.6; 95%CI: 1.4, 4.9; p=0.002]. HCC in our study affected a wide age range, mostly male, in advanced stage of disease, with no treatment and very low survival rates. Primary prevention should be advocated in view of late presentation and difficulty of treatment. Vaccination of hepatitis virus and avoidance of liver toxins are to be encouraged.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6023-6026
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• 2012

The incidence of hepatocellular carcinoma (HCC) in Malaysia for the year 2001 was 2.8 per 100,000 people. The mortality rate is increasing. A retrospective cohort study measuring the survival of HCC patients who received treatment in Selayang Hospital was conducted from 1 January 2003 to 31 December 2006. The main objectives of the study were to measure the survival of the patients and to understand the influencing factors, especially ethnicity. The subjects were newly diagnosed cases of HCC by CT scan and histopathological assessment who underwent futher investigations and treatments in Hospital Selayang (inception cohort). The survival time was measured from the date of diagnosis until the subjects died, or failed to follow-up at the end of the study period (31 December 2007). A total of 299 patients were selected with 95 patients dying, the majority among Chinese (39.1%). Subgroup analysis according to ethnicity proved significantly that Chinese patients who had smaller tumor, less number of nodules, low AFP level, Child Pugh Class A and received surgical treatment had a better median survival rate compared to other ethnic groups. Malay (cHR: 1.3, 95%CI; 0.89-1.85) and Indian (cHR: 1.3, 95%CI; 0.74-2.26) patients had a poor survival compared to Chinese patients, but not in the final model. Therefore ethnicity may play a role in survival of HCC patients, but not as a main hazard prognostic factor.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.13
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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.

• The Korean Journal of Physiology and Pharmacology
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• v.7 no.1
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• pp.29-31
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• 2003

It is well known that different expression of Apo-1/Fas (CD95) plays important roles in various tumors and hepatocellular carcinoma (HCC) pathogenesis. Apo-1/Fas mediated apoptosis is one of the important pathways of apoptosis and is known to mediate apoptotic cell death by fas ligand (FasL). To examine the possible relationship between Apo-1/Fas gene polymorphism and HCC susceptibility, MvaI restriction fragment length polymorphism (RFLP) of Apo-1/Fas gene was examined in 94 Korean HCC patients and 240 control subjects. No statistically significant difference in the genotypic distribution and allelic frequencies was found between the control and the HCC. It is, therefore, concluded that Apo-1/Fas gene polymorphism is not associated with HCC susceptibility. Further studies are needed in order to clarify the relationships between genotypes of Apo-1/Fas gene and HCC pathogenesis.

• Experimental and Molecular Medicine
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• v.50 no.11
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• pp.7.1-7.12
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• 2018

Recent findings from The Cancer Genome Atlas project have provided a comprehensive map of genomic alterations that occur in hepatocellular carcinoma (HCC), including unexpected mutations in apolipoprotein B (APOB). We aimed to determine the clinical significance of this non-oncogenetic mutation in HCC. An Apob gene signature was derived from genes that differed between control mice and mice treated with siRNA specific for Apob (1.5-fold difference; P < 0.005). Human gene expression data were collected from four independent HCC cohorts (n = 941). A prediction model was constructed using Bayesian compound covariate prediction, and the robustness of the APOB gene signature was validated in HCC cohorts. The correlation of the APOB signature with previously validated gene signatures was performed, and network analysis was conducted using ingenuity pathway analysis. APOB inactivation was associated with poor prognosis when the APOB gene signature was applied in all human HCC cohorts. Poor prognosis with APOB inactivation was consistently observed through cross-validation with previously reported gene signatures (NCIP A, HS, high-recurrence SNUR, and high RS subtypes). Knowledge-based gene network analysis using genes that differed between low-APOB and high-APOB groups in all four cohorts revealed that low-APOB activity was associated with upregulation of oncogenic and metastatic regulators, such as HGF, MTIF, ERBB2, FOXM1, and CD44, and inhibition of tumor suppressors, such as TP53 and PTEN. In conclusion, APOB inactivation is associated with poor outcome in patients with HCC, and APOB may play a role in regulating multiple genes involved in HCC development.