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Journal article

Correlation between centromere protein-F autoantibodies and cancer analyzed by enzyme-linked immunosorbent assay

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Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Artillerivej 5, 2300, Copenhagen S, Denmark1

Present address: LEO Pharma A/S, Industriparken 55, 2750, Ballerup, Denmark2

Department of Drug Design and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen Ø, Denmark3

Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, 2300, Copenhagen S, Denmark4

Department of Rheumatology, Frederiksberg Hospital, 2000, Frederiksberg, Denmark5

Centromere protein-F (CENP-F) is a large nuclear protein of 367 kDa, which is involved in multiple mitosis-related events such as proper assembly of the kinetochores, stabilization of heterochromatin, chromosome alignment and mitotic checkpoint signaling. Several studies have shown a correlation between CENP-F and cancer, e.g. the expression of CENP-F has been described to be upregulated in cancer cells.

Furthermore, several studies have described a significant correlation between the expression of autoantibodies to CENP-F and cancer. Autoantibodies to CENP-F were detected in a small number of samples during routine indirect immunofluorescence (IIF) analysis for anti-nuclear antibodies (ANA) using HEp-2 cells as substrate.

Using overlapping synthetic peptides covering a predicted structural maintenance of chromosomes (SMC) domain, we developed an enzyme-linked immunosorbent assay (ELISA) for detection of CENP-F antibodies. Analyzing the reactivity of the sera positive in IIF for CENP-F antibodies to overlapping CENP-F peptides, we showed that autoantibodies to several peptides correlate with the presence of antibodies to CENP-F and a diagnosis of cancer, as increased CENP-F antibody expression specific for malignant cancer patients to five peptides was found (A9, A12, A14, A16, A27).

These antibodies to CENP-F in clinical samples submitted for ANA analysis were found to have a positive predictive value for cancer of 50%. Furthermore, the expression of cancer-correlated CENP-F antibodies seemed to increase as a function of time from diagnosis. These results conform to previous findings that approximately 50% of those patients clinically tested for ANA analyses who express CENP-F antibodies are diagnosed with cancer, confirming that these antibodies may function as circulating tumor markers.

Thus, a peptide-based CENP-F ELISA focused on the SMC domain may aid in identifying individuals with a potential cancer.

Language: English
Publisher: BioMed Central
Year: 2013
Pages: 95-95
ISSN: 14764598
Types: Journal article
DOI: 10.1186/1476-4598-12-95
ORCIDs: Hansen, Paul Robert

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