Seromic profiling of ovarian and pancreatic cancer Journal Article


Authors: Gnjatic, S.; Ritter, E.; Büchler, M. W.; Giese, N. A.; Brors, B.; Frei, C.; Murray, A.; Halama, N.; Zörnig, I.; Chen, Y. T.; Andrews, C.; Ritter, G.; Old, L. J.; Odunsi, K.; Jäger, D.
Article Title: Seromic profiling of ovarian and pancreatic cancer
Abstract: Autoantibodies, a hallmark of both autoimmunity and cancer, represent an easily accessible surrogate for measuring adaptive immune responses to cancer. Sera can now be assayed for reactivity against thousands of proteins using microarrays, but there is no agreed-upon standard to analyze results. We developed a set of tailored quality control and normalization procedures based on ELISA validation to allow patient comparisons and determination of individual cutoffs for specificity and sensitivity. Sera from 60 patients with pancreatic cancer, 51 patients with ovarian cancer, and 53 age-matched healthy donors were used to assess the binding of IgG antibodies against a panel of >8000 human antigens using protein microarrays and fluorescence detection. The resulting data interpretation led to the definition and ranking of proteins with preferred recognition by the sera from cancer patients in comparison with healthy donors, both by frequency and strength of signal. We found that 202 proteins were preferentially immunogenic in ovarian cancer sera compared to 29 in pancreatic cancer, with few overlaps. Correlates of autoantibody signatures with known tumor expression of corresponding antigens, functional pathways, clinical stage, and outcome were examined. Serological analysis of arrays displaying the complete human proteome (seromics) represents a new era in cancer immunology, opening the way to defining the repertoire of the humoral immune response to cancer.
Keywords: adult; controlled study; aged; aged, 80 and over; middle aged; protein array analysis; major clinical study; case-control studies; cancer patient; pancreas cancer; pancreatic neoplasms; outcome assessment; sensitivity and specificity; ovarian neoplasms; biomarkers; quality control; proteome; reproducibility of results; ovary cancer; neoplasm proteins; tumor markers, biological; validation study; enzyme linked immunosorbent assay; antigen; immunogenicity; nucleotide sequence; autoantigen; antibody specificity; enzyme-linked immunosorbent assay; antigen binding; autoantibody; humoral immunity; fluorescence analysis; serum; autoantibodies; protein microarray; serology; signal detection; immunoglobulin g antibody; blood donors; protein microarrays; serum antibody; cancer immunology; genes, neoplasm
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 107
Issue: 11
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 2010-03-16
Start Page: 5088
End Page: 5093
Language: English
DOI: 10.1073/pnas.0914213107
PUBMED: 20194765
PROVIDER: scopus
PMCID: PMC2841879
DOI/URL:
Notes: --- - "Cited By (since 1996): 11" - "Export Date: 20 April 2011" - "CODEN: PNASA" - "Source: Scopus"
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MSK Authors
  1. Anne Murray
    3 Murray
  2. Sacha Gnjatic
    113 Gnjatic
  3. Gerd Ritter
    166 Ritter
  4. Erika Ritter
    37 Ritter
  5. Lloyd J Old
    593 Old