N-linked glycan structures and their expressions change in the blood sera of ovarian cancer patients.
N-linked glycan structures and their expressions change in the blood sera of ovarian cancer patients.
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DOI：
10.1021/pr201070k
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发表时间：
2012-04-06
影响因子：
4.4
通讯作者：
Novotny, Milos V.
中科院分区：
文献类型：
--
作者：
Alley, William R., Jr.;Vasseur, Jacqueline A.;Goetz, John A.;Syoboda, Martin;Mann, Benjamin F.;Matei, Daniela E.;Menning, Nancy;Hussein, Ahmed;Mechref, Yehia;Novotny, Milos V.
糖基化蛋白在广泛的生物化学和生物学过程中发挥重要作用，并且先前的报告已经表明蛋白质糖基化的变化发生在癌症的发生和进展期间。卵巢癌（OC）是一种致命的恶性肿瘤，最常在发生转移后诊断。因此，早期发现OC是提高生存率的关键。为此，已经提出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。在本研究中，我们将这一概念扩展到OC。为了表征总N-聚糖水平的差异，将20名健康对照女性提供的血清样本与从诊断为晚期复发性OC的患者获得的血清样本进行比较，这些患者在接受治疗之前（N = 19）和一个月后，在第二个治疗周期之前（N = 11）参加了实验性治疗试验。此外，还对IgG相关N-聚糖进行了分析，并对核心岩藻糖基化与外臂岩藻糖基化的相对丰度水平进行了表征。N-连接的糖组学图谱显示，与对照组相比，OC样本中具有不同程度唾液酸化和岩藻糖基化的三分支和四分支结构的丰度增加，并且“二等分”聚糖的水平明显降低。在源自IgG的N-连接聚糖上观察到α-半乳糖基化结构水平增加，这与岩藻糖残基的存在无关。在OC样本中也发现了外臂岩藻糖基化水平升高。这些结果允许对照样品在接受实验治疗之前与基线卵巢癌患者区分开。在某些情况下，治疗前样品可以与实验治疗后样品区分开，因为这些患者中的许多显示出疾病的进一步进展。
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-galactosylated 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.
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影响因子：
7.4
作者：
Alley, William R., Jr.;Madera, Milan;Mechref, Yehia;Novotny, Milos V.
通讯作者：
Novotny, Milos V.
影响因子：
3.4
作者：
Abbott KL;Lim JM;Wells L;Benigno BB;McDonald JF;Pierce M
通讯作者：
Pierce M
DOI：
10.1158/1078-0432.ccr-07-5261
发表时间：
2009-03-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Goldman R;Ressom HW;Varghese RS;Goldman L;Bascug G;Loffredo CA;Abdel-Hamid M;Gouda I;Ezzat S;Kyselova Z;Mechref Y;Novotny MV
通讯作者：
Novotny MV
影响因子：
3.5
作者：
Higai, Koji;Miyazaki, Noriko;Matsumoto, Kojiro
通讯作者：
Matsumoto, Kojiro
影响因子：
3.1
作者：
Jankovic, Miroslava M.;Milutinovic, Bojana S.
通讯作者：
Milutinovic, Bojana S.