Seromic analysis of antibody responses in non-small cell lung cancer patients and healthy donors using conformational protein arrays Journal Article

Authors: Gnjatic, S.; Wheeler, C.; Ebner, M.; Ritter, E.; Murray, A.; Altorki, N. K.; Ferrara, C. A.; Hepburne-Scott, H.; Joyce, S.; Koopman, J.; McAndrew, M. B.; Workman, N.; Ritter, G.; Fallon, R.; Old, L. J.
Article Title: Seromic analysis of antibody responses in non-small cell lung cancer patients and healthy donors using conformational protein arrays
Abstract: Analysis of antibody responses to self-antigens has driven the development of the field of tumor immunology, with the identification of many protein targets found in cancer but with limited expression in normal tissues. Protein microarray technologies offer an unprecedented platform to assay the serological response of cancer patients to tumor antigens in a comprehensive fashion, against many proteins simultaneously. We developed an array containing 329 full-length proteins, originally identified as antigenic in various cancer patients by serological expression cloning (SEREX), that were immobilized as folded, functional products accessible for antibody binding. To validate the use of these microarrays, we selected 31 sera from non-small cell lung cancer patients previously known to react to the following antigens by ELISA: LAGE-1/CTAG2, MAGEA4, TP53, SSX and SOX2. These sera were compared with 22 sera from healthy donors for reactivity against a series of antigens present on microarrays. The sensitivity and specificity of the arrays compared favorably with standard ELISA techniques (94% concordance). We present here a stringent strategy for data analysis and normalization that is applicable to protein arrays in general, and describe findings suggesting that this approach is suitable for defining potential antigenic targets for cancer vaccine development, serum antibody signatures with clinical value, characterization of predictive serum markers for experimental therapeutics, and eventually for the serological definition of the cancer proteome (seromics). © 2008 Elsevier B.V. All rights reserved.
Keywords: controlled study; protein array analysis; major clinical study; cancer patient; comparative study; sensitivity and specificity; protein conformation; lung non small cell cancer; carcinoma, non-small-cell lung; lung neoplasms; enzyme linked immunosorbent assay; antigens, neoplasm; tumor antigens; antibody response; data analysis; predictive value of tests; protein folding; elisa; antigen binding; data normalization; igg; serum and plasma profiling; validation; protein microarray; serology; antibodies, neoplasm
Journal Title: Journal of Immunological Methods
Volume: 341
Issue: 1-2
ISSN: 0022-1759
Publisher: Elsevier Science, Inc.  
Date Published: 2009-02-28
Start Page: 50
End Page: 58
Language: English
DOI: 10.1016/j.jim.2008.10.016
PUBMED: 19041653
PROVIDER: scopus
Notes: --- - "Cited By (since 1996): 6" - "Export Date: 30 November 2010" - "CODEN: JIMMB" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Anne Murray
    3 Murray
  2. Sacha Gnjatic
    111 Gnjatic
  3. Gerd Ritter
    158 Ritter
  4. Erika Ritter
    34 Ritter
  5. Lloyd J Old
    386 Old