title: Correlation between centromere protein-F autoantibodies and cancer analyzed by enzyme-linked immunosorbent assay.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Artillerivej 5, 2300, Copenhagen S, Denmark. gh@ssi.dk.
authors: Simon
authors: S
authors: Welner
authors: Nicole Hartwig
authors: NH
authors: Trier
authors: Morten
authors: M
authors: Frisch
authors: Henning
authors: H
authors: Locht
authors: Paul Robert
authors: PR
authors: Hansen
authors: Gunnar
authors: G
authors: Houen
mesh_terms: D001323:Autoantibodies / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002868:Chromosomal Proteins, Non-Histone / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D008840:Microfilament Proteins / Q000276:immunology*; D015999:Multivariate Analysis; D009369:Neoplasms / Q000097:blood* / Q000276:immunology; D025341:Principal Component Analysis
chemical_list: D001323:Autoantibodies; D014408:Biomarkers, Tumor; D002868:Chromosomal Proteins, Non-Histone; D008840:Microfilament Proteins; C094772:centromere protein F
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