癌化における血清糖蛋白糖鎖変異の臨床的意義とそのmolecular basis,アルファフェトプロテインのフコシル化糖鎖変異を中心に

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The quantitative determinations of alpha-fetoprotein (AFP) has been extensively used for the detection of hepatocellular carcinoma (HCC). However, the serum concentration of AFP also increases in neoplastic diseases of gastrointestinal tract metastatic to the liver and nonneoplastic liver diseases. Moreover, the serum concentrations of AFP in HCC at the time of initial diagnosis became lower recently owing to the advancement of imaging modalities. These clinical circum-stances have lead to the need of molecular discrimination of AFP between these diseases. This has been attained by determining the carbohydrate structures of AFP with the reactivity to the lectins, Lens culinaris agglutinin (LCA) and concanavalin A (Con A). The percentage of LCA-reactive species of AFP is higher in HCC than in benign liver diseases with statistical significance. The alphal-6 fucosylation of sugar chain at innermost N-acetylglucosamine is molecular basis of this variation. Therefore, the terms "fucosylation index" have been introduced to express the percentages of LCA-reactive species of AFP. This index is useful for the diagnosis of HCC even if the carcinoma is at an early stage. Furthermore, they seem to serve the prediction of HCC in the follow-up course of chronic liver diseases. On the other hand, Con A-nonreactive species of AFP was significantly higher in AFP-producing gastrointestinal carcinoma than HCC and benign liver diseases. Molecular basis of Con A-nonreactive variants is the N-acetylglu-cosaminylation of the mannose residue at the trimannosyl core although the position to be modified is different. Therefor, the terms "fucosylation and glucosaminylation indices" were adopted to express the percentages of LCA-reactive and Con A-nonreactive species of AFP, respectively. Thus, not only qualitative but also quantitative measurements provide us very valuable information in the differential diagnosis of various AFP-producing diseases.
新潟大学の論文
2003-11-10

癌化における血清糖蛋白糖鎖変異の臨床的意義とそのmolecular basis,アルファフェトプロテインのフコシル化糖鎖変異を中心に

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