GalNAcalpha1-3Gal, a new prognostic marker for cervical cancer.

GalNAcalpha1-3Gal, a new prognostic marker for cervical cancer.
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DOI:
10.1002/ijc.24716
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发表时间:
2010-01-15
影响因子:
6.4
通讯作者:
Gildersleeve, Jeffrey C.
Gildersleeve, Jeffrey C.
中科院分区:
医学1区
文献类型:
--
作者:
Li, Qian;Anver, Miriam R.;Li, Zhitao;Butcher, Donna O.;Gildersleeve, Jeffrey C.

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Cancer cells undergo significant changes in carbohydrate expression, and these alterations can be useful as biomarkers and therapeutic targets. In this study, we investigated the expression of carbohydrate antigens containing a terminal GalNAcα1-3Gal or GalNAcα1-6Gal on human cervix and cervical carcinoma. Monoclonal antibodies to each of these carbohydrates were generated by immunizing rabbits with the corresponding antigen conjugated to KLH followed by hybridoma production. Antibodies were screened and evaluated using a combination of carbohydrate microarray profiling, ELISA, dot blot and immunohistochemical staining to verify specificity. Antibody 132-3 was found to selectively recognize GalNAcα1-3Gal with little cross-reactivity to other structurally similar antigens such as GalNAcα1-6Gal, blood group A, Forssman antigen and the Tn antigen on both solution assays and human tissue. While GalNAcα1-6Gal expression was not detected, GalNAcα1-3Gal expression was found on 55% of squamous cell carcinomas. Expression in normal tissue was observed but was restricted to the suprabasal epithelial layer. Importantly, we found expression of the antigen on cervical cancer had a statistically significant correlation with the 5-year survival rate of the patients (48% vs 85% for antigen neg. vs pos., p = 0.017). Expression of GalNAcα1-3Gal did not correlate with other clinical factors including tumor stage, size, and lymph node metastasis, indicating the antigen is a new, independent biomarker for the prognosis of cervical cancer.
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