AIM: To clone and identify the differentially expressed gene fragments in hepatocellular carcinoma (HCC) and normal liver tissues and to explore the molecular pathogenesis of HCC.

METHODS: Fluorescent mRNA differential display (mRNA-DD) was used to compare the differential gene expression in HCC and normal liver tissue samples. The obtained gene fragments were cloned and sequenced. The sequences were submitted to the GenBank for homologue analysis using BLAST software. RT-PCR was performed to detect the expression of each differential gene fragment in HCC and normal tissue samples.

RESULTS: Gel imaging scan revealed a 500-600 bp differential gene fragment. The sequence of this gene fragment was compared with that in GenBank, showing that this gene fragment was homologous to EEG1 (99%). RT-PCR demonstrated that the expression of this gene fragment was significantly lower in HCC tissue samples than in normal tissue samples (P = 0.001).

CONCLUSION: EEG1 gene expression is much lower in HCC tissue than in normal tissue. Its down-regulated expression in HCC tissues is probably related to the carcinogenesis of HCC.

• Hepatocellular carcinoma
• mRNA differential display
• Gene cloning

AIM: To assess whether a correlation exists between oxidative DNA damage occurring in chronic HCV-related hepatitis and expression levels of pro-inflammatory cytokines, TGF-α and c-myc.

METHODS: The series included 37 patients with chronic active HCV-related hepatitis and 11 with HCV-related compensated cirrhosis. Eight-hydroxydeoxyguanosine in liver biopsies was quantified using an electrochemical detector. The mRNA expression of TNF-α, IL-1β, TGF-α and c-myc in liver specimens was detected by semi-quantitative comparative RT-PCR.

RESULTS: TNF-α levels were significantly higher in hepatitis patients than in cirrhosis patients (P = 0.05). IL-1β was higher in cirrhosis patients (P = 0.05). A significant correlation was found between TNF-α and staging (P = 0.05) and between IL-1β levels and grading (P = 0.04). c-myc showed a significantly higher expression in cirrhosis patients (P = 0.001). Eight-hydroxydeoxyguanosine levels were significantly higher in cirrhosis patients (P = 0.05) and in HCV genotype 1 (P = 0.03). Considering all patients, 8-hydroxydeoxyguanosine levels were found to be correlated with genotype (P = 0.04) and grading (P = 0.007). Also multiple logistic regression analysis demonstrated a significant correlation among the number of DNA adducts, TNF-α expression and HCV genotype (P = 0.02).

CONCLUSION: In chronic HCV-related liver damage, oxidative DNA damage correlates with HCV genotype, grading and TNF-α levels. As HCV-related liver damage progresses, TNF-α levels drop while IL-1β and c-myc levels increase, which may be relevant to liver carcinogenesis.

• Oxidative DNA damage
• Chronic HCV-related hepatitis
• Inflammatory mediators

• Adult
• Cell Proliferation
• Cytokines/genetics
• DNA Damage
• Female
• Hepatitis C, Chronic/metabolism
• Hepatitis C, Chronic/pathology
• Humans
• Liver Cirrhosis/metabolism
• Liver Cirrhosis/pathology
• Male
• Middle Aged
• Oxidation-Reduction
• Proto-Oncogene Proteins c-myc/genetics
• RNA, Messenger/analysis
• Transforming Growth Factor alpha/genetics

AIM: To investigate the serum level and expression of insulin growth factor II (IGF-II) in liver tissues of rats with early experimental hepatocellular carcinomas (HCC) and its significance in early diagnosis.

METHODS: Early experimental hepatocellular carcinomas were induced by diethylnitrosamine (DENA) in 180 male SD rats. Another 20 male SD rats served as control. The IGF-II serum level was measured by ELISA. Immunohistochemistry and electron microscopic immunohistochemistry were used to observe the expression of IGF-II in normal and tumor liver tissues and its ultrastructural location in malignant hepatocytes. The expressions of IGF-II in human hepatoma cell lines HepG2, SMMC7721 and human embryonic liver cell line L-02 were measured by immunocytochemistry. IGF-II mRNA level was studied by in situ hybridization.

RESULTS: IGF-II was expressed in the cytoplasm of both sinusoidal cells in paracancerous cirrhotic liver tissue and malignant hepatocytes in early experimental HCC tissues. Gold particles were seen on the rough endoplasmic reticulum and the mitochondrion in malignant hepatocytes. IGF-II was expressed in the human hepatoma cell lines. The mRNA level of IGF-II was higher in rat liver tumor tissue than in normal rat liver tissue. The serum IGF-II level of the early experimental HCC group was 34.67 ± 10.53 ng·mL^-1 and that of the control group was 11.75 ± 5.84 ng·mL^-1. The rank sum test was used for statistical analysis. There was a significant difference between the two groups (P < 0.01).

CONCLUSION: During the induction of early experimental HCC by DENA, IGF-II may promote hepatocytic proliferation via a paracrine mechanism in the pre-cancerous stage. When hepatocytes are transformed into malignant cells, they may secrete IGF-II and promote malignant cell proliferation by an autocrine mechanism. IGF-II may be a possible biological marker in the early diagnosis of HCC.

• Animals
• Humans
• Insulin-Like Growth Factor II/metabolism
• Liver Neoplasms, Experimental/diagnosis
• Liver Neoplasms, Experimental/metabolism
• Male
• Rats
• Rats, Sprague-Dawley
• Time Factors
• Tumor Cells, Cultured/metabolism