• 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.15 no.17
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• pp.7069-7077
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• 2014

Background: This retrospective study aimed to validate the safety and effectiveness of hepatectomy for huge hepatocellular carcinoma (HCC). Materials and Methods: Data of patients who underwent hepatectomy for HCC between January 2006 and December 2012 were reviewed. The patients were divided into three groups: huge HCC(${\geq}10cm$ in diameter), large HCC(${\geq}5$ but<10 cm in diameter) and small HCC(<5cm in diameter). Results: Characteristics of pre-operative patients in all three groups were homogeneously distributed except for alpha fetal protein (AFP)(p<0.001).The 30, 60, 90-day post-operative mortality rates were not different among the three groups (p=0.785, p=0.560, and p=0.549). Laboratory data at 1, 3, and 7 days after surgery also did not vary. The 5-year overall survival (OS) and 5-year disease-free survival (DFS) rates in the huge and large HCC groups were lower than that of the small HCC group (OS: 32.5% vs 36.3% vs 71.2%, p=0.000; DFS: 20.0% vs 24.8% vs 40.7%, p=0.039), but there was no difference between the huge and large HCC groups (OS: 32.5% vs 36.3%, p=0.667; DFS: 20.0% vs 24.8%, p=0.540). In multivariate analysis, five independent poor prognostic factors that affected OS were significantly associated with worse survival (p<0.05), namely, AFP level, macrovascular invasion, Edmondsone Steiner grade, surgical margin and Ishak score. AFP level, macrovascular invasion, microvascular invasion, and surgical margin influenced disease-free survival independently (p<0.05). Conclusions: The safety of hepatectomy for huge HCC is similar to that for large and small HCC; and this approach for huge HCC may achieve similar long-term survival and disease-free survival as for large HCC.

• BMB Reports
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• v.52 no.4
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• pp.277-282
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• 2019

Currently speaking, it is noted that radiofrequency ablation (RFA) has been the most widely used treatment for hepatocellular carcinoma (HCC) occurring in patients. However, accumulating evidence has demonstrated that the incidence of insufficient RFA (IRFA) may result in the identified rapid progression of residual HCC in the patient, which can greatly hinder the effectiveness and patient reported benefits of utilizing this technique. Although many efforts have been proposed, the underlying mechanisms triggering the rapid progression of residual HCC after IRFA have not yet been fully clarified through current research literature reviews. It was shown in this study that cell proliferation, migration and invasion of residual HepG2 and SMMC7721 cells were significantly increased after the IRFA was simulated in vitro. In other words, it is noted that IRFA could do this by enhancing the image of autophagy of the residual HCC cell via the $HIF-1{\alpha}/BNIP3$ pathway. Consequently, the down-regulation of BNIP3 may result in the inhibition of the residual HCC cell progression and autophagy after IRFA. Our present study results suggest that IRFA could promote residual HCC cell progression in vitro by enhancing autophagy via the $HIF-1{\alpha}/BNIP3$ pathway. For this reason, it is noted that the targeting of the BNIP3 may be useful in preventing the rapid growth and metastasis of residual HCC after IRFA.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.4103-4107
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• 2015

Background: Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide. Transarterial chemoembolisation (TACE) is the standardized therapy for intermediate stage HCC. However, the prognosis for HCC patients treated by TACE greatly varies. Thus, there is a critical need for finding biomarkers to predict the prognosis of HCC patients. The amino acid transporter-2 (ASCT2) is involved in tumorigenesis and progression of many malignancies. This study aimed to evaluate the predictive role of two single nuclear polymorphisms (SNPs, rs3826793 and rs2070246) in the ASCT2 gene in HCC patients treated by TACE. Materials and Methods: Two functional SNPs (rs3826793 and rs2070246) in the ASCT2 gene were selected and genotyped using the Sequenom iPLEX genotyping system in a cohort of 448 unresectable Chinese HCC patients treated by TACE. Univariate and multivariate Cox proportional hazards models and Kaplan-Meier curves were used for the prognosis analyses. Results: There was no significant association between two SNPs (rs3826793 and rs2070246) in the ASCT2 gene and overall survival of TACE treated HCC patients. However, we demonstrated that patients with early stage HCC carrying T genotype in rs2070246 showed better OS than those carrying CC genotype (P=0.023). Conclusions: We demonstrated that patients with early stage HCC carrying T genotype in rs2070246 showed better OS than those carrying CC genotype.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4417-4421
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• 2012

Objective: The results from studies on associations of the glutathione S-transferase T1 (GSTT1) gene polymorphism and hepatocellular carcinoma (HCC) risk in Chinese populations are still conflicting. This meta-analysis was performed to evaluate the relationship in detail. Methods: Eligible reports were recruited into this meta-analysis from the databases of PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database). Results were expressed with odds ratios (OR) for dichotomous data, and 95% confidence intervals (CI) were also calculated. Results: Eighteen investigations were identified for the analysis of association between polymorphic deletion of GSTT1 and HCC, consisting of 2,693 patients with HCC and 4,696 controls. Null genotype of GSTT1 was associated with HCC susceptibility in Chinese (OR=1.53, 95%CI: 1.28-1.82; P<0.00001). Conclusion: The GSTT1 null genotype is associated with HCC susceptibility in Chinese.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.885-889
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• 2013

microRNAs (miRNAs) are small non-coding RNAs that regulate gene expression through post-transcriptional interactions with mRNA. miRNAs have recently emerged as key regulators of various cancers. Although miR-27a has been implicated in several other cancers, its role in hepatitis B virus-related hepatocellular carcinoma (HCC) is unknown. In this study, we showed miR-27a to be frequently up-regulated in HCC tissues and HCC cell lines (HepG2 and Huh7). Overexpression of miR-27a enhanced cell proliferation, promoted migration and invasion, and activated cell cycling in HepG2 and Huh7 cells. In summary, our results suggest that up-regulation of miR-27a may play an oncogenic role in the development of HCC and might thus be a new therapeutic target in HCC patients.

• 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.

• BMB Reports
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• v.45 no.11
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• pp.629-634
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• 2012

The human glycoprotein, stanniocalcin 2 (STC2) plays multiple roles in several tumor types, however, its function and clinical significance in hepatocellular carcinoma (HCC) remain unclear. In this study, we detected STC2 expression by quantitative real-time PCR and found STC2 was upregulated in HCC tissues, correlated with tumor size and multiplicity of HCC. Ectopic expression of STC2 markedly promoted HCC cell proliferation and colony formation, while silencing of endogenous STC2 resulted in a reduced cell growth by cell cycle delay in G0/G1 phase. Western blot analysis demonstrated that STC2 could regulate the expression of cyclin D1 and activate extracellular signal-regulated kinase 1/2 (ERK1/2) in a dominant-positive manner. Transwell chamber assay also indicated altered patterns of STC2 expression had an important effect on cell migration. Our findings suggest that STC2 functions as a potential oncoprotein in the development and progression of HCC as well as a promising molecular target for HCC therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1297-1303
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• 2012

Aims: Primary hepatocellular carcinoma (HCC) is a common malignancy often related to hepatitis viral infection. Smad4 is known to mediate the TGF-${\beta}$ pathway to suppress tumorigenesis. However, the function of Smad4 in HCC is still controversial. In this study we compared levels of Smad4 in HCC tissues with or without hepatitis virus infection and adjacent normal-appearing liver. Methods: Samples from HCC patients were analyzed for Smad4 protein and mRNA expression by immunohistochemistry (IHC), RT-PCR and Western blotting. Results: We found that tumor tissues expressed less Smad4 mRNA and protein than the adjacent tissues. Most HCC tumor tissues were negative for Smad4 in IHC staining, while the majority of adjacent tissues were positively stained. Interestingly, protein levels were higher in HCC tissues with viral hepatitis than those without virus infection. Suppression of expression appeared closely related to HCC, so that Smad4 appears to function as a tumor suppressor gene (TSG). Conclusion: Patients with hepatitis viral infection, at higher risk for HCC, exhibited increased Smad4 protein expression suggesting hepatitis virus may modulate Smad4 expression, which is functionally distinct from its putative role as a TSG. Smad4 expression may thus be an applicable marker for diagnosis and/or a target to develop therapeutic agents for HCC.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3479-3483
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• 2015

Objective: Patients with hepatocellular carcinoma (HCC) in stage Barcelona Clinic Liver Cancer (BCLC)-A were grouped based on whether they were accompanied with hepatitis B virus (HBV) infection or not so as to explore the clinical characteristics and prognostic conditions of HCC patients with non-HBV/hepatitis C virus (HCV). Materials and Methods: Clinical data of 64 stage BCLC-A HCC patients with non-HBV/HCV infection (observation group) who received radical hepatectomy in the Affiliated Cancer Hospital of Guangxi Medical University from January, 2006 to November, 2014 were retrospectively analyzed and compared with those of 409 stage BCLC-A HCC patients with HBV infection (control group) in corresponding period. Results: The postoperative 1-, 3- and 5-year recurrent rates of the observation group were 25%, 38.6% and 48.8%, with postoperative mean and median disease-free survival time being 49.1 months and 62.0 months, respectively. Additionally, the postoperative 1-, 3- and 5-year survival rates of observation group were 90.1%, 72.7% and 62.0%, with the mean and median survival times being 54.4 months and 70.0 months, respectively. Conclusions: The 1-year recurrent rate is the highest in HCC patients with non-HBV/HCV, and almost half of the patients have recurrence within 1 year, after which the recurrent rate decreases along with the time.