Abstract
BMI-1 is overexpressed in a variety of cancers, which can elicit an immune response leading to the induction of autoantibodies. However, BMI-1 autoantibody as a biomarker has seldom been studied with the exception of nasopharyngeal carcinoma. Whether BMI-1 autoantibodies can be used as a biomarker for cervical carcinoma is unclear. In this study,BMI-1 proteins were isolated by screening of a T7 phage cDNA library from mixed cervical carcinoma tissues. We analyzed BMI-1 autoantibody levels in serum samples from 67 patients with cervical carcinoma and 65 controls using ELISA and immunoblot. BMI-1 mRNA or protein levels were over-expressed in cervical carcinoma cell lines. Immunoblot results exhibited increased BMI-1 autoantibody levels in patient sera compared to normal sera. Additionally, the results for antibody affinity assay showed that there was no difference between cervical polyps and normal sera of BMI-1 autoantibody levels, but it was significantly greater in patient sera than that in normal controls (patient 0.827±0.043 and normal 0.445±0.023; P<0.001). What's more, the levels of BMI-1 autoantibody increased significantly at stage I (0.672±0.019) compared to normal sera (P<0.001), and levels of BMI-1 autoantibodies were increased gradually during the tumor progression (stage I 0.672±0.019; stage II 0.775 ±0.019; stage III 0.890 ±0.027; stage IV 1.043±0.041), which were significantly correlated with disease progression of cervical carcer (P<0.001). Statistical analyses using logistic regression and receiver operating characteristics (ROC) curves indicated that the BMI-1 autoantibody level can be used as a biomarker for cervical carcinoma (sensitivity 0.78 and specificity 0.76; AUC = 0.922). In conclusion, measuring BMI-1 autoantibody levels of patients with cervical cancer could have clinical prognostic value as well as a non-tissue specific biomarker for neoplasms expressing BMI-1.
Highlights
Cervical cancanoma is much more deadly in developing countries than in developed countries [1]
We analyzed the expression of BMI-1 in several human cervical carcinoma cell lines using Reverse transcription-PCR (RT-PCR) or Western blot
A number of studies indicate that one or more oncogenic types of human papilloma virus (HPV) may be responsible for cervical cancer, which is supported by strong epidemiological evidence and the detection of HPV DNA in 90–100% of cervical cancers [19]
Summary
Cervical cancanoma is much more deadly in developing countries than in developed countries [1]. BMI-1-deficient mouse embryonic fibroblasts (MEF) overexpress INK4a/ARF locus–encoded genes, p16INK4a and p19ARF (mouse homologue of human p14ARF) and undergo premature senescence in culture [9,10] Proper function of this family is maintaining gene expression patterns during development. BMI-1 is associated with both humoral and T-cell responses, suggesting that it represents a novel family of tumor-associated antigens (TAAs) that might be potential target for immunotherapy [14,15]. New biomarkers, such as autoantibody signatures, may improve the early detection of cervical carcinoma. We further evaluated the sensitivity and specificity of ELISA for predicting cervical carcinoma
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