The levels and clinical significances of hepatocyte growth factor in the hepatic tissue and serum of hepatocellular carcinoma

Abstract

Objective To investigate hepatocyte growth factor (HGF) levels in the tissue and serum of patients with chronic hepatitis, cirrhosis or hepatocellular carcinoma (HCC), and analyze the clinical significances of HGF for HCC. Method Surgical specimens from 97 patients were collected during Dec.2003 to Aug.2008 in the Third Central Hospital.The patients were prospectively enrolled and categorized into four groups:normal subjects (n=11), chronic hepatitis B or C (n=6), cirrhosis (n=20) and HCC (n= 60) including well-differentiated (n= 21), moderately differentiated (n= 23), poorly differentiated (n= 16) specimens.N0 (n=24), N1 (n=21), N2 (n=54) and N3 (n=43) were tissues respectively removed from liver at 0, 1, 2 or 3 cm beyond the margin of tumor.HGF mRNA expression in liver tissues was determined by real-time quantitative reverse transcription- (RT)-PCR.Serum HGF levels in the other cases of normal subjects (n=20), chronic hepatitis B or C (n=20), cirrhosis (n=20) and HCC (n=57) were measured by ELISA.The Kaplan-Meier method with log-rank test was employed for survival analysis.Univariate and multivariate analyses were performed to identify prognostic factors in each group. Results The HGF mRNA in normal subjects, chronic hepatitis, cirrhosis, N3, N2, N1, N0 and HCC were 0.99(0.78-1.66), 2.15(1.06-3.40), 1.78(1.18-2.73), 4.59(2.67-8.63), 3.86(2.25-6.45)，3.12(1.59-5.74), 2.92(0.88-5.99) and 0.48(0.19-1.06) respectively.The serum concentration of HGF in the normal subjects, chronic hepatitis, cirrhosis and HCC patients were (0.31±0.05), (0.65±0.07), (1.27±0.30) and （2.06±0.66） μg/L respectively.The highest level of HGF mRNA was found in N3, while the HGF mRNA expression in HCC was ［（2.14±0.52）μg/L］ lower than that not only in the non-tumor tissues, but also in the normal control (U=196.50, P=0.03).The serum concentration of HGF was significantly higher in patients with chronic hepatitis, cirrhosis or HCC than in normal subjects.The serum HGF level of HCC was bounced after hepatectomy (t=2.70, P＜0.01).On the logistic regression analysis，the tumor numbers and Child-pugh were related with the levels of the tissue HGF mRNA and serum HGF of HCC, OR were 0.15 (95%CI：0.03-0.72, P<0.05) and 0.13 (95%CI：0.27-0.89, P<0.05), respectively.Univariate analysis using the Cox proportional hazards model in the complication groups revealed that the levels of the tissue HGF mRNA and serum HGF were significant risk factors of death for HCC, OR were 0.02 (95%CI:0.00-0.52, P<0.05) and 10.01 (95%CI:1.16-86.23, P< 0.05), respectively.On the Log-rank analysis, no statistically difference in the cumulative survival was found between the two groups categorized by median (0.49) of tissue HGF mRNA 2-ΔΔCT (χ2=0.13，P=0.72). While the HCC patients were dichotomized by their the median(0.69 μg/L) of serum HGF concentration, the death risk for the patients with higher levels of HGF was increased 2.84 fold than those with lower levels (95%CI:1.03-7.92，P<0.05). Conclusion HGF mRNA expression is decreased in tumor tissues, while its level in tumor adjacent live and serum is significantly elevated and is in association with shortened postoperative survival of HCC patients.（Chin J Lab Med,2012,35:598-603） Key words: Liver neoplasms; Carcinoma，hepatocellular; Hepatocyte growth factor; Reverse transcription-quantitative polymerase chain; Enzyme-linked immunosorbent assay