title: Possible contribution of circulating transforming growth factor-beta1 to immunity and prognosis in unresectable hepatocellular carcinoma.
abstract: Transforming growth factor-beta1 (TGF-beta1) 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-beta1 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-beta1 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-beta1 concentration is a predictor of outcome of patients with unresectable HCC. Circulating TGF-beta1 supposedly contributes to the suppression of anti-tumor immunity in the advanced disease.
authors.affiliation: Second Department of Internal Medicine, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Okumoto
authors.forename: Etsuko
authors.initials: E
authors.lastname: Hattori
authors.forename: Kazuko
authors.initials: K
authors.lastname: Tamura
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kiso
authors.forename: Hisayoshi
authors.initials: H
authors.lastname: Watanabe
authors.forename: Koji
authors.initials: K
authors.lastname: Saito
authors.forename: Takafumi
authors.initials: T
authors.lastname: Saito
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Togashi
authors.forename: Sumio
authors.initials: S
authors.lastname: Kawata
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000276:immunology*; D005260:Female; D006801:Humans; D007109:Immunity; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008113:Liver Neoplasms / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D011237:Predictive Value of Tests; D011379:Prognosis; D016019:Survival Analysis; D016212:Transforming Growth Factor beta / Q000097:blood / Q000276:immunology*; D053773:Transforming Growth Factor beta1
chemical_list: C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1