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新型单链抗体GD3A10确定了一种卵巢癌硫酸软骨素生物标志物。

Novel single-chain antibody GD3A10 defines a chondroitin sulfate biomarker for ovarian cancer.

作者信息

Vallen Myrtille J E, van Tilborg Angela A G, Tesselaar Maria H, ten Dam Gerdy B, Bulten Johan, van Kuppevelt Toin H, Massuger Leon F A G

机构信息

Department of Biochemistry, Nijmegen Center for Molecular Life Sciences, PO Box 9101, 6500 HB Nijmegen, The Netherlands.

出版信息

Biomark Med. 2014;8(5):699-711. doi: 10.2217/bmm.14.6.

Abstract

AIMS

Ovarian cancer has the highest case-to-fatality-index of all gynecological cancers. In this study, tumor-related alterations in the extracellular matrix, especially regarding chondroitin sulfate glycosaminoglycans, are proposed as a novel biomarker in ovarian cancer.

MATERIALS & METHODS: Phage display technology was applied to select antibody GD3A10, which was obtained by biopanning using embryonic glycosaminoglycans as a source for carcinogenic antigens. GD3A10 antigen specificity was studied in situ using glycosaminoglycan degrading enzymes. A patient cohort (n = 159) was immunohistochemically stained. Scoring was correlated with clinical prognostic parameters and survival. Normal rat organs were used to study normal antigen distribution.

RESULTS

GD3A10 is a specific anti-chondroitin sulfate antibody and the epitope was absent or very restricted in normal rat organs, normal ovaries and benign ovarian tumors. Strong stromal expression was observed in malignant ovarian tumors, and correlated with poor prognostic factors such as subtype, tumor grade and recurrence.

CONCLUSION

tumor-associated glycosaminoglycans are an interesting source of biomarkers in ovarian cancer, as shown here using chondroitin sulfate antibody GD3A10.

摘要

目的

卵巢癌在所有妇科癌症中具有最高的病例致死率。在本研究中,细胞外基质中与肿瘤相关的改变,尤其是硫酸软骨素糖胺聚糖方面的改变,被提议作为卵巢癌的一种新型生物标志物。

材料与方法

应用噬菌体展示技术筛选抗体GD3A10,该抗体通过以胚胎糖胺聚糖作为致癌抗原来源进行生物淘选获得。使用糖胺聚糖降解酶原位研究GD3A10的抗原特异性。对一个患者队列(n = 159)进行免疫组织化学染色。评分与临床预后参数及生存率相关。使用正常大鼠器官研究正常抗原分布。

结果

GD3A10是一种特异性抗硫酸软骨素抗体,在正常大鼠器官、正常卵巢和良性卵巢肿瘤中该表位不存在或非常有限。在恶性卵巢肿瘤中观察到强基质表达,且与诸如亚型、肿瘤分级和复发等不良预后因素相关。

结论

肿瘤相关糖胺聚糖是卵巢癌中一种有趣的生物标志物来源,如本研究中使用硫酸软骨素抗体GD3A10所显示的那样。

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