Prognostic utility of serum alpha-N-acetylgalactosaminidase and immunosuppression resulted from deglycosylation of serum Gc protein in oral cancer patients.
Vitamin D3-binding protein (Gc protein), a serum glycoprotein, is the precursor for the macrophage activating factor. Cancer patient sera contain alpha-N-acetylgalactosaminidase that deglycosylates Gc protein. Deglycosylated Gc protein cannot be converted to macrophage activating factor, leading to immunosuppression. Of 46 oral cancer patients with squamous cell carcinoma, approximately 22% had greatly reduced precursor activities. The precursor activity of approximately 61% of these patients was moderately reduced. The remaining patients (17%) had precursor activities equivalent to those of healthy humans. Patients with low precursor activity of serum Gc protein had high serum alpha-N-acetylgalactosaminidase activity. In contrast, patients with high precursor activity had low serum alpha-N-acetylgalactosaminidase activity. Thus, levels of serum alpha-N-acetylgalactosaminidase of individual patients have an inverse correlation with precursor activities of their serum Gc protein. Surgical removal of tumors resulted in a subtle decrease in serum alpha-N-acetylgalactosaminidase activity with concomitant increase in the precursor activity of serum Gc protein. Serum enzyme analysis of nude mice transplanted with a human oral squamous carcinoma cell line revealed that serum alpha-N-acetylgalactosaminidase activity is directly proportional to tumor burden. Thus, alpha-N-acetylgalactosaminidase activity in patient bloodstream can serve as a diagnostic/prognostic index.
Yamamoto
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Laboratory of Cancer Immunology and Molecular Biology, Albert Einstein Cancer Center, Philadelphia, Pennsylvania 19141, USA.
Naraparaju
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Urade
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D000818:Animals; D000951:Antigens, Neoplasm / Q000097:blood; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000473:pathology; D005260:Female; D006031:Glycosylation; D006596:Hexosaminidases / Q000097:blood*; D006801:Humans; D007165:Immunosuppression Therapy; D016215:Macrophage-Activating Factors / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000097:blood / Q000378:metabolism*; D011379:Prognosis; D015843:Serpins; D014809:Vitamin D-Binding Protein / Q000097:blood / Q000378:metabolism*; D048809:alpha-N-Acetylgalactosaminidase
D000951:Antigens, Neoplasm; D016215:Macrophage-Activating Factors; D009363:Neoplasm Proteins; D015843:Serpins; D014809:Vitamin D-Binding Protein; C051072:squamous cell carcinoma-related antigen; D006596:Hexosaminidases; C482722:NAGA protein, human; D048809:alpha-N-Acetylgalactosaminidase