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Autoantibodies to Annexin XI-A and Other Autoantigens in the Diagnosis of Breast Cancer.

Department of Internal Medicine, Division of Rheumatology, Wayne Stste University, 4201 St. Antoine Boulevard, Detroit, MI 48201, USA. .
Cancer Research (Impact Factor: 9.28). 09/2004; 64(15):5089-96. DOI: 10.1158/0008-5472.CAN-03-0932
Source: PubMed

ABSTRACT We report on the identification of autoantigens commonly recognized by sera from patients with breast cancer. We selected ten sera from patients with invasive ductal carcinoma (IDC) of the breast with high titer IgG autoantibodies for biopanning of a T7 phage breast cancer cDNA display library. A high throughput method involved the assembly of 938 T7 phages encoding potential breast cancer autoantigens. Microarrays of positive phages were probed with sera from 90 patients with breast cancer [15 patients with ductal carcinoma in situ (DCIS) and 75 patients with IDC of the breast], with 51 non-cancer control sera and with sera from 21 patients with systemic autoimmune diseases. A 12-phage breast cancer predictor group was constructed with phage inserts recognized by sera from patients with breast cancer and not by non-cancer or autoimmune control sera (P < 0.0001). Several autoantigens including annexin XI-A, the p80 subunit of the Ku antigen, ribosomal protein S6, and other unknown autoantigens could significantly discriminate between breast cancer and non-cancer control sera. Biopanning with three different sera led to the cloning of partial cDNA sequences identical to annexin XI-A. IgG autoantibodies reacting with the amino acid 41-74 sequence of annexin XI-A were found in 19% of all women with breast cancer but in 60% of sera from women with DCIS of the breast. In addition, partial sequences identical to annexin XI-A, nucleolar protein interacting with the forkhead-associated (FHA) domain of pKi-67, the KIAA1671 gene product, ribosomal protein S6, cyclin K, elongation factor-2, Grb2-associated protein 2, and other unknown proteins could distinguish DCIS from IDC of the breast and appear to be potential biomarkers for the diagnosis of breast cancer.

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    • "The corresponding tumour auto-antibodies could be used as biomarkers for early diagnosis and prognosis of cancer (Anderson & LaBaer 2005, Casiano et al. 2006, Sanchez-Carbayo 2006). Proteins like ANXA11, p53, HIP1 and ECPKA are known to serve as TAA biomarkers for various cancers (Bradley et al. 2005, Fernandez-Madrid et al. 2004, Nesterova et al. 2006, Soussi 2000). Tomaino et al. (2007) used Western blot analysis to identify autoantibodies against pancreatic ductal adenocarcinoma (PDAC) associated antigens from the PDAC sera. "
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    ABSTRACT: Aberrantly expressed proteins in tumours evoke an immunological response. These immunogenic proteins can serve as potential biomarkers for the early diagno-sis of cancers. In this study, we performed a candidate marker screen on macroarrays containing 38,016 hu-man proteins, derived from a human fetal-brain expres-sion library, with the pools of sera from breast cancer patients (1 pool of benign samples, 3 pools of ductal carcinoma and 2 pools of lobular carcinoma) and 1 pool of sera from healthy women. A panel of 642 sero-reactive clones were deduced from these macroarray experiments which include 284 in-frame clones. Over-representation analyses of the sero-reactive in-frame clones enabled the identification of the sets of genes over-expressed in various pathways of the functional categories (KEGG, Transpath, Pfam and GO). Protein microarrays, generated using the His-tag proteins de-rived from the macroarray experiments, were used to evaluate the sera from breast cancer patients (24 malig-nant, 16 benign) and 20 control individuals. Using the PAM algorithm we elucidated a panel of 50 clones which enabled the correct classification prediction of 93% of the breast-nodule positive group (benign & malignant) sera from healthy individuals' sera with 100% sensitivity and 85% specificity. This was fol-lowed by over-representation analysis of the signifi-cant clones derived from the class prediction.
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    • "An approach to address this challenge is the identification of a large number of tumor antigens that can be used both for therapy and for diagnosis. Lately, immunogenic antigens have been combined to define autoantibody signatures that have been reported for a variety of cancers including prostate, lung, ovarian, and brain cancers [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19]. Recently, we identified 35 antigens that allowed detecting a specific autoantibody signature of glioma [12]. "
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    ABSTRACT: Seroreactivity profiling emerges as valuable technique for minimal invasive cancer detection. Recently, we provided first evidence for the applicability of serum profiling of glioma using a limited number of immunogenic antigens. Here, we screened 57 glioma and 60 healthy sera for autoantibodies against 1827 Escherichia coli expressed clones, including 509 in-frame peptide sequences. By a linear support vector machine approach, we calculated mean specificity, sensitivity, and accuracy of 100 repetitive classifications. We were able to differentiate glioma sera from sera of the healthy controls with a specificity of 90.28%, a sensitivity of 87.31% and an accuracy of 88.84%. We were also able to differentiate World Health Organization grade IV glioma sera from healthy sera with a specificity of 98.45%, a sensitivity of 80.93%, and an accuracy of 92.88%. To rank the antigens according to their information content, we computed the area under the receiver operator characteristic curve value for each clone. Altogether, we found 46 immunogenic clones including 16 in-frame clones that were informative for the classification of glioma sera versus healthy sera. For the separation of glioblastoma versus healthy sera, we found 91 informative clones including 26 in-frame clones. The best-suited in-frame clone for the classification glioma sera versus healthy sera corresponded to the vimentin gene (VIM) that was previously associated with glioma. In the future, autoantibody signatures in glioma not only may prove useful for diagnosis but also offer the prospect for a personalized immune-based therapy.
    Neoplasia (New York, N.Y.) 12/2009; 11(12):1383-9. DOI:10.1593/neo.91018 · 5.40 Impact Factor
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    • "Annexin XI is a member of the annexin superfamily of Ca 2+ signal transduction proteins associated with cell growth and differentiation. This study [30] reports on the identification of autoantigens commonly recognized by sera from patients with breast cancer. They selected 10 sera from patients with invasive ductal carcinoma (IDC) of the breast with high titer IgG autoantibodies for biopanning of a T7 phage breast cancer DNA display library. "
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    ABSTRACT: By definition, tumor biomarkers are selective molecules that can distinguish between patients with cancer and controls. Serum tumor markers have been the most widely used approach for cancer detection. However, the limitations of these markers, which are based on the measurement of tumor antigens, preclude their general use in cancer screening and diagnosis. Here we give an overview of recent cancer biomarker developments based on the detection of autoantibodies produced against tumor antigens in patients' sera. This new detection method can measure the autoantibodies for a spectrum of tumor antigens in a single assay, with sensitivity and specificity exceeding those obtained using the conventional antigen determination method. Autoantibodies against serum cancer biomarkers offer a novel technology for cancer detection.
    Biochimica et Biophysica Acta 07/2006; 1762(6):587-91. DOI:10.1016/j.bbadis.2006.04.001 · 4.66 Impact Factor
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