Possible contribution of circulating transforming growth factor-β1 to immunity and prognosis in unresectable hepatocellular carcinoma
Article first published online: 18 FEB 2004
Volume 24, Issue 1, pages 21–28, February 2004
How to Cite
Okumoto, K., Hattori, E., Tamura, K., Kiso, S., Watanabe, H., Saito, K., Saito, T., Togashi, H. and Kawata, S. (2004), Possible contribution of circulating transforming growth factor-β1 to immunity and prognosis in unresectable hepatocellular carcinoma. Liver International, 24: 21–28. doi: 10.1111/j.1478-3231.2004.00882.x
- Issue published online: 18 FEB 2004
- Article first published online: 18 FEB 2004
- Received 22 July 2003,accepted 20 September 2003
- lymphokine-activated killer (LAK) activity;
- natural killer (NK) activity;
- prognostic marker;
Transforming growth factor-β1 (TGF-β1) has been implicated in tumor progression. The relationship of this cytokine as measured in plasma to anti-tumor immunity and prognosis was investigated.
This study consisted of 70 consecutive patients with unresectable hepatocellular carcinoma (HCC) (median age, 65 years). Forty-four healthy age-matched subjects and 32 patients with cirrhosis but no carcinoma served as controls. Patients with HCC were divided into those with plasma TGF-β1 concentrations above (group A, n=21) or below (group B, n=49) 10 ng/ml (the mean concentration+2SD in the concentrations of the controls with cirrhosis was 8.7 ng/ml).
Age, gender, Child-Pugh grade, and tumor stage distributions were similar in groups A and B. Considering all tumor stages together and individually, group A had a significantly shorter survival (median for all stages, 2 months) than group B (median for all stages, 10 months; P<0.01, generalized Wilcoxon's test). Groups A and B had significantly shorter survival than controls with cirrhosis (P<0.001 for each). Lymphokine-activated killer (LAK) activity in group A was significantly lower than that in group B (P<0.001). Natural killer (NK) activity in group A was also significantly lower than that in group B (P<0.05). Plasma TGF-β1 concentration was a significant predictor of survival by Cox's proportional-hazards regression analysis (multivariate analysis, P<0.01). LAK and NK activities were also weak but significant predictors (P<0.05 and <0.05, respectively).
These data suggest that plasma TGF-β1 concentration is a predictor of outcome of patients with unresectable HCC. Circulating TGF-β1 supposedly contributes to the suppression of anti-tumor immunity in the advanced disease.