Glycosylation status of serum immunoglobulin G in patients with prostate diseases

Abstract

Occurrences of high values in patients with benign prostate disease and low values in patients with highly suspicious cancer have diminished the trustworthiness of prostate-specific antigen as an early diagnostic marker of prostate cancer. In the search for other complimentary markers, we focused on serum IgG from patients with prostate diseases as well as normal subjects. IgG purified from the sera of normal control subjects and patients with prostate diseases, was digested with peptide N-glycanase. Released glycans were quantified using MALDI-time of flight mass spectrometry. We report that N-linked (N-acetylhexosamine)₂(deoxyhexose)(mannose)₃(N-acetylglucosamine)₂ was significantly increased in the IgG heavy chains of patients with prostate cancer compared with that of either benign prostatic disease patients or healthy subjects, whereas (hexose)(N-acetylhexosamine)₂(deoxyhexose)(mannose)₃ (N-acetylglucosamine)₂ was more abundant in the heavy chains of healthy subjects and benign prostatic disease patients. Thus, an absence of the terminal hexose of N-linked glycans has been closely connected to the progression of prostate cancer. Furthermore, surface plasmon resonance analyses have revealed that IgG from patients with prostate cancer has a decreased binding for Sambucus nigra lectin, compared with that from the benign prostatic disease patients or from normal subjects, suggesting lower levels of (N-acetylneuraminic acid)(α2-6)galactose/N-acetylgalactosamine groups in the N-linked glycans of patient IgG. Meanwhile, wheat germ agglutinin binding to IgG of the cancer group was significantly larger than that for the benign prostatic disease group but smaller than that for normal subjects. Our study indicates that the glycosylation changes in IgG can become useful diagnostic parameters for prostate cancer.

We report that N-linked (N-acetylhexosamine)2(deoxyhexose)(mannose)3(N-acetylglucosamine)2 was significantly increased in the serum IgG heavy chains of patients with prostate cancer compared with that of either benign prostatic disease patients or healthy normal subjects, whereas (hexose)(N-acetylhexosamine)2(deoxyhexose)(mannose)3 (N-acetylglucosamine)2 was more abundant in the heavy chains of healthy subjects and benign prostatic disease patients. Thus, an absence of the terminal hexose of N-linked glycans has been closely connected to the progression of prostate cancer.

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