Autoantibodies to annexin XI-A and other autoantigens in the diagnosis of breast cancer

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 hi...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2004-08, Vol.64 (15), p.5089-5096
Main Authors: FERNANDEZ-MADRID, Félix, NAIMEI TANG, ALANSARI, Huda, GRANDA, José L, TAIT, Larry, AMIRIKIA, Kathryn C, MOROIANU, Mihail, XIAOJU WANG, KARVONEN, Robert L
Format: Article
Language:English
Subjects:
Annexins - immunology
Antibodies, Monoclonal
Antineoplastic agents
Autoantibodies - blood
Autoantigens - immunology
Autoimmune Diseases - immunology
Autoimmune Diseases - metabolism
Autoimmune Diseases - pathology
Biological and medical sciences
Breast Neoplasms - diagnosis
Carcinoma, Ductal, Breast - diagnosis
Carcinoma, Intraductal, Noninfiltrating - diagnosis
Female
Humans
Medical sciences
Middle Aged
Peptide Library
Pharmacology. Drug treatments
Tumors
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Summary: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.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.can-03-0932