Department of Chemistry, Indiana University, Bloomington, Indiana, United States.
J Proteome Res. 2012 Apr 6;11(4):2282-300. doi: 10.1021/pr201070k. Epub 2012 Mar 7.
Glycosylated proteins play important roles in a broad spectrum of biochemical and biological processes, and prior reports have suggested that changes in protein glycosylation occur during cancer initiation and progression. Ovarian cancer (OC) is a fatal malignancy, most commonly diagnosed after the development of metastases. Therefore, early detection of OC is key to improving survival. To this end, specific changes of the serum glycome have been proposed as possible biomarkers for different types of cancers. In this study, we extend this concept to OC. To characterize differences in total N-glycan levels, serum samples provided by 20 healthy control women were compared to those acquired from patients diagnosed with late-stage recurrent OC who were enrolled in an experimental treatment trial prior to receiving therapy (N=19) and one month later, prior to the second treatment cycle (N=11). Additionally, analyses of the N-glycans associated with IgG and characterization of the relative abundance levels of core vs outer-arm fucosylation were also performed. The N-linked glycomic profiles revealed increased abundances of tri- and tetra-branched structures with varying degrees of sialylation and fucosylation and an apparent decrease in the levels of "bisecting" glycans in OC samples compared to controls. Increased levels of a-galactosylation structures were observed on N-linked glycans derived from IgG, which were independent of the presence of fucose residues. Elevated levels of outer-arm fucosylation were also identified in the OC samples. These results allowed the control samples to be distinguished from the baseline ovarian cancer patients prior to receiving the experimental treatment. In some cases, the pre-treatment samples could be distinguished from the post-experimental treatment samples, as many of those patients showed a further progression of the disease.
糖基化蛋白在广泛的生化和生物学过程中发挥着重要作用，先前的研究表明，蛋白质糖基化的变化发生在癌症的起始和进展过程中。卵巢癌（OC）是一种致命的恶性肿瘤，大多数在发生转移后才被诊断出来。因此，OC 的早期检测是提高生存率的关键。为此，已经提出了血清糖组的特定变化作为不同类型癌症的可能生物标志物。在这项研究中，我们将这一概念扩展到 OC。为了描述总 N-聚糖水平的差异，我们将 20 名健康对照女性的血清样本与在接受治疗前（N=19）和第二个治疗周期前一个月（N=11）接受实验性治疗试验的晚期复发性 OC 患者的血清样本进行了比较。此外，还对与 IgG 相关的 N-聚糖进行了分析，并对核心与外臂岩藻糖基化的相对丰度水平进行了表征。N-连接糖组学分析显示，与对照组相比，OC 样本中三分支和四分支结构的丰度增加，且具有不同程度的唾液酸化和岩藻糖基化，而“双分支”糖的水平似乎降低。在源自 IgG 的 N-连接糖上观察到α-半乳糖基化结构的水平升高，这与岩藻糖残基的存在无关。在 OC 样本中还鉴定到外臂岩藻糖基化水平升高。这些结果使得在接受实验性治疗之前，可以将对照样本与基线 OC 患者区分开来。在某些情况下，与治疗后样本相比，治疗前样本可以区分出来，因为许多患者的疾病进一步进展。
