Center for Glycomics, Departments of Cellular and Molecular Medicine and Oral Diagnostics, University of Copenhagen, Blegdamsvej 3, Copenhagen 2200 N, Denmark.
Cancer Res. 2010 Feb 15;70(4):1306-13. doi: 10.1158/0008-5472.CAN-09-2893. Epub 2010 Feb 2.
Autoantibodies to cancer antigens hold promise as biomarkers for early detection of cancer. Proteins that are aberrantly processed in cancer cells are likely to present autoantibody targets. The extracellular mucin MUC1 is overexpressed and aberrantly glycosylated in many cancers; thus, we evaluated whether autoantibodies generated to aberrant O-glycoforms of MUC1 might serve as sensitive diagnostic biomarkers for cancer. Using an antibody-based glycoprofiling ELISA assay, we documented that aberrant truncated glycoforms were not detected in sera of cancer patients. An O-glycopeptide microarray was developed that detected IgG antibodies to aberrant O-glycopeptide epitopes in patients vaccinated with a keyhole limpet hemocyanin-conjugated truncated MUC1 peptide. We detected cancer-associated IgG autoantibodies in sera from breast, ovarian, and prostate cancer patients against different aberrent O-glycopeptide epitopes derived from MUC1. These autoantibodies represent a previously unaddressed source of sensitive biomarkers for early detection of cancer. The methods we have developed for chemoenzymatic synthesis of O-glycopeptides on microarrays may allow for broader mining of the entire cancer O-glycopeptidome.
自身抗体对抗原具有癌症作为癌症早期检测的生物标志物有很大的希望。在癌细胞中异常加工的蛋白质很可能成为自身抗体的靶标。细胞外粘蛋白 MUC1 在许多癌症中过度表达和异常糖基化；因此，我们评估了针对 MUC1 异常 O-糖型产生的自身抗体是否可以作为癌症的敏感诊断生物标志物。我们使用基于抗体的糖蛋白组学 ELISA 测定法证明，在癌症患者的血清中未检测到异常截断的糖型。开发了一种 O-糖肽微阵列，该微阵列可检测用与截断的 MUC1 肽缀合的 keyhole limpet hemocyanin 接种的患者中针对异常 O-糖肽表位的 IgG 抗体。我们针对源自 MUC1 的不同异常 O-糖肽表位，从乳腺癌、卵巢癌和前列腺癌患者的血清中检测到与癌症相关的 IgG 自身抗体。这些自身抗体代表了一种以前未被关注的用于癌症早期检测的敏感生物标志物来源。我们开发的用于在微阵列上进行化学酶合成 O-糖肽的方法可能允许更广泛地挖掘整个癌症 O-糖肽组。
