Background The sugar-chain structures of circulating alpha-fetoproteinin patients with hepatocellular carcinomas differ from thosein patients with cirrhosis. We studied the reactivity of alpha-fetoproteinwith two lectins, Lens culinaris agglutinin A and erythroagglutinatingphytohemagglutinin, to monitor the evolution of hepatocellularcarcinoma in patients with cirrhosis.
Methods Among 361 patients with cirrhosis caused mainly by chronichepatitis B or hepatitis C virus infection, 33 with base-lineserum alpha-fetoprotein concentrations 30 ng per milliliterwere found to have hepatocellular carcinomas during a mean follow-upof 35 months. The lectin-reactive profiles of the alpha-fetoproteinin the serum of these 33 patients were analyzed and comparedwith those in the serum of 32 patients with cirrhosis who hadincreased base-line serum alpha-fetoprotein concentrations andwere followed for at least 24 months but in whom hepatocellularcarcinoma did not develop.
Results At the time of tumor detection, 24 (73 percent) of the33 patients with cirrhosis and hepatocellular carcinoma hadhigher percentages of L. culinaris agglutinin A-reactive alpha-fetoprotein(alpha-fetoprotein L3), erythroagglutinating phytohemagglutinin-reactivealpha-fetoprotein (alpha-fetoprotein P4+P5), or both than the32 patients with cirrhosis but no hepatocellular carcinoma.Among the 24 patients, one or both of the markers were firstelevated 3 to 18 months before the hepatocellular carcinomawas detected by imaging techniques.
Conclusions Measurements of the alpha-fetoprotein L3 and alpha-fetoproteinP4+P5 fractions of serum alpha-fetoprotein allow the differentiationof hepatocellular carcinoma from cirrhosis in some cases andserve as predictive markers for the development of hepatocellularcarcinoma during the follow-up of patients with cirrhosis.
Source Information
From the First Department of Internal Medicine, Nagasaki University School of Medicine (Y.S., K.N., Y.K., M.S., S.N.), and the Health Research Center, Nagasaki University (N.I., T.K.), both in Nagasaki; the Department of Public Health, Okayama University Medical School, Okayama (K.T.); and Sanraku Hospital, Tokyo (Y.E.) -- all in Japan.
Address reprint requests to Dr. Nagataki at the First Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852, Japan.
Henry, L, Lavabre-Bertrand, T, Vercambre, L, Ramos, J, Carillo, S, Guiraud, I, Pouderoux, P, Bismuth, M, Valats, J-C, Demattei, C, Duny, Y, Chaze, I, Funakoshi, N, Bureau, J P, Daures, J-P, Blanc, P
(2009). Plasma proteasome level is a reliable early marker of malignant transformation of liver cirrhosis. Gut
58: 833-838
[Abstract][Full Text]
Nakano, M., Higo, D., Arai, E., Nakagawa, T., Kakehi, K., Taniguchi, N., Kondo, A.
(2009). Capillary electrophoresis-electrospray ionization mass spectrometry for rapid and sensitive N-glycan analysis of glycoproteins as 9-fluorenylmethyl derivatives. Glycobiology
19: 135-143
[Abstract][Full Text]
Kuno, A., Kato, Y., Matsuda, A., Kaneko, M. K., Ito, H., Amano, K., Chiba, Y., Narimatsu, H., Hirabayashi, J.
(2009). Focused Differential Glycan Analysis with the Platform Antibody-assisted Lectin Profiling for Glycan-related Biomarker Verification. Mol. Cell. Proteomics
8: 99-108
[Abstract][Full Text]
Zinkin, N. T., Grall, F., Bhaskar, K., Otu, H. H., Spentzos, D., Kalmowitz, B., Wells, M., Guerrero, M., Asara, J. M., Libermann, T. A., Afdhal, N. H.
(2008). Serum Proteomics and Biomarkers in Hepatocellular Carcinoma and Chronic Liver Disease. Clin. Cancer Res.
14: 470-477
[Abstract][Full Text]
Wang, X., Gu, J., Ihara, H., Miyoshi, E., Honke, K., Taniguchi, N.
(2006). Core Fucosylation Regulates Epidermal Growth Factor Receptor-mediated Intracellular Signaling. J. Biol. Chem.
281: 2572-2577
[Abstract][Full Text]
Guan, M., Rodriguez-Madoz, J. R., Alzuguren, P., Gomar, C., Kramer, M. G., Kochanek, S., Prieto, J., Smerdou, C., Qian, C.
(2006). Increased Efficacy and Safety in the Treatment of Experimental Liver Cancer with a Novel Adenovirus-Alphavirus Hybrid Vector. Cancer Res.
66: 1620-1629
[Abstract][Full Text]
Hertl, M., Cosimi, A. B.
(2005). Liver Transplantation for Malignancy. The Oncologist
10: 269-281
[Abstract][Full Text]
Ling, C.-Q., Li, B., Zhang, C., Zhu, D.-Z., Huang, X.-Q., Gu, W., Li, S.-X.
(2005). Inhibitory effect of recombinant adenovirus carrying melittin gene on hepatocellular carcinoma. Ann Oncol
16: 109-115
[Abstract][Full Text]
Yoon, S. K., Lim, N. K., Ha, S.-A., Park, Y. G., Choi, J. Y., Chung, K. W., Sun, H. S., Choi, M. J., Chung, J., Wands, J. R., Kim, J. W.
(2004). The Human Cervical Cancer Oncogene Protein Is a Biomarker for Human Hepatocellular Carcinoma. Cancer Res.
64: 5434-5441
[Abstract][Full Text]
Martinez-Duncker, I., Michalski, J.-C., Bauvy, C., Candelier, J.-J., Mennesson, B., Codogno, P., Oriol, R., Mollicone, R.
(2004). Activity and tissue distribution of splice variants of {alpha}6-fucosyltransferase in human embryogenesis. Glycobiology
14: 13-25
[Abstract][Full Text]
Noda, K., Miyoshi, E., Gu, J., Gao, C.-X., Nakahara, S., Kitada, T., Honke, K., Suzuki, K., Yoshihara, H., Yoshikawa, K., Kawano, K., Tonetti, M., Kasahara, A., Hori, M., Hayashi, N., Taniguchi, N.
(2003). Relationship between Elevated FX Expression and Increased Production of GDP-L-Fucose, a Common Donor Substrate for Fucosylation in Human Hepatocellular Carcinoma and Hepatoma Cell Lines. Cancer Res.
63: 6282-6289
[Abstract][Full Text]
Benson III, A. B., Mitchell, E., Abramson, N., Klencke, B., Ritch, P., Burnham, J. P., McGuirt, C., Bonny, T., Levin, J., Hohneker, J.
(2002). Oral eniluracil/5-fluorouracil in patients with inoperable hepatocellular carcinoma. Ann Oncol
13: 576-581
[Abstract][Full Text]
Okada, S.
(2001). Cancer Chemoprevention as Adjuvant Therapy for Hepatocellular Carcinoma. Jpn J Clin Oncol
31: 357-358
[Full Text]
Ido, A., Uto, H., Moriuchi, A., Nagata, K., Onaga, Y., Onaga, M., Hori, T., Hirono, S., Hayashi, K., Tamaoki, T., Tsubouchi, H.
(2001). Gene Therapy Targeting for Hepatocellular Carcinoma: Selective and Enhanced Suicide Gene Expression Regulated by a Hypoxia-inducible Enhancer Linked to a Human {{alpha}}-Fetoprotein Promoter. Cancer Res.
61: 3016-3021
[Abstract][Full Text]
Wang, W., Li, W., Ikeda, Y., Miyagawa, J.-I., Taniguchi, M., Miyoshi, E., Sheng, Y., Ekuni, A., Ko, J. H., Yamamoto, Y., Sugimoto, T., Yamashita, S., Matsuzawa, Y., Grabowski, G. A., Honke, K., Taniguchi, N.
(2001). Ectopic expression of {{alpha}}1,6 fucosyltransferase in mice causes steatosis in the liver and kidney accompanied by a modification of lysosomal acid lipase. Glycobiology
11: 165-174
[Abstract][Full Text]
Tradati, F., Colombo, M., Mannucci, P.M., Rumi, M.G., De Fazio, C., Gamba, G., Ciavarella, N., Rocino, A., Morfini, M., Scaraggi, A., Taioli, E., Italian Hemophilia Centers, t. S. G. o. t. A. o.
(1998). A Prospective Multicenter Study of Hepatocellular Carcinoma in Italian Hemophiliacs With Chronic Hepatitis C. Blood
91: 1173-1177
[Abstract][Full Text]
Muto, Y., Moriwaki, H., Ninomiya, M., Adachi, S., Saito, A., Takasaki, K. T., Tanaka, T., Tsurumi, K., Okuno, M., Tomita, E., Nakamura, T., Kojima, T., The Hepatoma Prevention Study Group,
(1996). Prevention of Second Primary Tumors by an Acyclic Retinoid, Polyprenoic Acid, in Patients with Hepatocellular Carcinoma. NEJM
334: 1561-1568
[Abstract][Full Text]
(1993). A NEW ALPHA-FETOPROTEIN MEASUREMENT AIDS LIVER CANCER DIAGNOSIS. JWatch General
1993: 7-7
[Full Text]
30 ng per milliliter were found to have hepatocellular carcinomas during a mean follow-up of 35 months. The lectin-reactive profiles of the alpha-fetoprotein in the serum of these 33 patients were analyzed and compared with those in the serum of 32 patients with cirrhosis who had increased base-line serum alpha-fetoprotein concentrations and were followed for at least 24 months but in whom hepatocellular carcinoma did not develop. 
Previous
