α1-antitrypsin and survival in hepatocellular carcinoma

Abstract

Summary The association between serum levels of alpha,-antitrypsin (a,AT) at the time of diagnosis and survival was studied in a group of 78 patients with confirmed hepatocellular carcinoma (HCC). All 78 patients were followed until the time of death, which occurred in all instances from HCC, with a median time of 6 months and a range of 1-117 months. Cox's proportional hazards model was utilised in the analysis controlling for sex, age, HBsAg status and logarithmically transformed values of a-fetoprotein (ax-FP). Older patients and patients positive for HBsAg have suggestively higher fatality rates (0.05 <P <0.10) whereas in these data sex and AFP levels were not important prognostic factors. Increased levels of serum a xEAT at the time of diagnosis of HCC were statistically significantly (P <0.05) related with shorter survival, patients with higher serum a,AT by 200 mg 100 ml-' having an expected survival time shorter by about 25%. a,-Antitrypsin (o,AT) is the main protease inhibitor in human serum and its most important biological function is to inactivate a variety of proteolytic enzymes, particularly leukocyte elastase (Harpel, 1983;Cohen, 1986). Individuals who are homozygous for the Z allele are at an increased risk for hepatocellular carcinoma (HCC) (Eriksson et al., 1986), but there is no convincing evidence that individuals who are heterozygous for the Z allelle, and other alleles associated with mjAT deficiency, are over-represented among cases of HCC (Govindarajan et al., 1981;Sparos et al., 1984;Eriksson, 1985;Marwick et al., 1985;Schneider et al., 1986). Interestingly, several authors have confirmed the observation of Kew et al. (1978) that HCC cases have elevated levels of serum a,AT, an increase which is found across several a,AT phenotypes (Chio & Oon, 1979;Matsuzaki et al., 1981). In 1984 we reported the results of a relatively large epidemiological study in Greece exploring, among other issues, the association between a,AT levels and HCC, by hepatitis B virus (HBV) serological status (Sparos et al., 1984). Since then, we have been able to follow, until the time of death, 78 out of the 80 cases with HCC included in that study, and we report here the findings concerning the association between serum levels of a,AT and survival of these patients. Patients and methodsIn the original study (Trichopoulos et al., 1978) al., 1978, 1980). Serum levels and phenotypes of a,AT were determined by radial immunodiffusion and electrofocusing in acrylamide gel, respectively (Vesterberg, 1973;Chapuis-Cellier, 1975 (Cox, 1972), using survival time (there were no censored observations), sex (male = 1, female = 2), age (in decades), HBsAg status (negative = 1, positive = 2), serum a,AT levels (in 100mg 100 ml-') and serum a-FP levels (in ng ml-' after log transformation) as model variables. Cox's model allows the estimation of the patients' instantaneous fatality rate ratio (and associated confidence intervals), con There is evidence that the fatality rate from HCC is higher among older persons and among patien...

Analysis of Differentially Expressed Proteins in Colorectal Cancer Using Hydroxyapatite Column and SDS-PAGE

“…This finding is in agreement with Zhang et al [61]. A1AT is the main serine protease inhibitor in human serum that inactivates numerous of proteolytic enzymes by forming stable complexes with the enzymes [62]. The relationship of A1AT level with various types of cancer had been previously reported [63][64][65].…”

Gene expression profiles in primary pancreatic tumors and metastatic lesions of Ela-c-myc transgenic mice

“…Therefore, the expression of proteinase inhibitors is considered to be an anti-malignant event. Serpina1, a major inhibitor of human serine proteases in serum, is produced mainly by the liver, but also by extra-hepatic cells, including neutrophils and certain cancer cells [ 51 , 52 ]. However, clinical studies have shown that high circulating levels of Serpina1 directly correlate with tumor progression [ 53 , 54 ].…”

Alpha‐fetoprotein production by hepatocellular carcinoma is prognostic of poor patients survival

“…It has been shown that the serum AFP level may predict the prognosis of patients with HCC [2,3]. At present, the serum AFP concentration is shown to be useful not only in diagnosing HCC, but also as a prognostic indicator [4,51. The serum AFP is occasionally negative in patients with HCC [6] and can also be detected in non-malignant disease [7].…”

“…Alpha-fetoprotein (AFP) is a useful serum marker for hepatocellular carcinoma (HCC) [ 11 and the sequential measurement of AFP is useful for the postoperative evaluation of patients who undergo hepatectomy for HCC. It has been shown that the serum AFP level may predict the prognosis of patients with HCC [2,3]. At present, the serum AFP concentration is shown to be useful not only in diagnosing HCC, but also as a prognostic indicator [4,51. The serum AFP is occasionally negative in patients with HCC [6] and can also be detected in non-malignant disease [7].…”