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

ABSTRACT: 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 GalNAcalpha1-3Gal or GalNAcalpha1-6Gal 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 GalNAcalpha1-3Gal with little cross-reactivity to other structurally similar antigens such as GalNAcalpha1-6Gal, blood group A, Forssman antigen and the Tn antigen on both solution assays and human tissue. Although GalNAcalpha1-6Gal expression was not detected, GalNAcalpha1-3Gal 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 negative vs. positive, p = 0.017). Expression of GalNAcalpha1-3Gal 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.

SUBMITTER: Li Q

PROVIDER: S-EPMC2794947 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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

Li Qian Q Anver Miriam R MR Li Zhitao Z Butcher Donna O DO Gildersleeve Jeffrey C JC

International journal of cancer 20100101 2

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 GalNAcalpha1-3Gal or GalNAcalpha1-6Gal 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 ...[more]

PMID: 19585575

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Project description:It has been confirmed that the systemic inflammation response index (SIRI) based on peripheral blood neutrophil, monocyte and lymphocyte counts can be used for the prognostication of patients with various malignant tumors. However, the prognostic value of SIRI in cervical cancer patients has not yet been reported. This study found that a higher SIRI was related to lymphovascular invasion and was also significantly associated with FIGO stage, radiotherapy, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and monocyte/lymphocyte ratio (MLR) but not related to other clinical and pathological parameters. According to the Kaplan-Meier survival analysis, a high SIRI was associated with the poor prognosis of cervical cancer patients in the primary and validation groups. SIRI, NLR, PLR, and MLR can all be used to determine the prognosis of patients with operable cervical cancer. Moreover, it was confirmed that only SIRI was an independent prognostic factor for patients with operable cervical cancer. The same result was obtained in the propensity score matching (PSM) analysis. In the ROC curve analysis, SIRI was more accurate in predicting the prognosis of cervical cancer patients. Then, a nomogram was established based on SIRI, FIGO stage and lymphovascular invasion, which could determine the prognosis of cervical cancer patients more accurately than FIGO stage. The validation cohort showed the same results. In addition, the changes in SIRI relative to the baseline value at 4-8 weeks after surgery were closely related to the survival of cervical cancer patients. Compared with those with unchanged SIRI (absolute value of variation <25%), cervical cancer patients with an increase in SIRI > 75% had worse OS (P < 0.001), while patients with a decrease in SIRI > 75% had a better prognosis (P < 0.001). SIRI can serve as a new independent prognostic index and a potential marker for therapeutic response monitoring in patients with curable cervical cancer. Compared with the traditional FIGO staging system, the nomogram integrating SIRI can predict the survival of cervical cancer patients more objectively and reliably after radical surgery.

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

Publications

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

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