Molecular Diagnosis & Therapy

, Volume 14, Issue 3, pp 149–154

Identification of Cancer Autoantigens in Serum

Toward Diagnostic/Prognostic Testing?
Leading Article


The development of noninvasive screening tests would represent a major advance in the fight against cancer, as pre-clinical or early diagnosis could be considered the best weapons to reduce cancer mortality. The use of autoantibodies against cancer autoantigens is a promising alternative to fulfill this goal. Recent progress in protein microarray formats and other proteomic strategies has brought extraordinary opportunities to advance the discovery of new cancer autoantigens. These new approaches have allowed identification of autoantibodies with a higher prevalence, simplifying the development of predictor panels with wider coverage. Still, some issues have to be resolved before clinical application of these results. First, technical limitations in the quality and reproducibility of the microarrays and the statistical tools for data analysis have to be resolved. Second, thorough validation of the candidate biomarkers has to be carried out to include not just one particular cancer type but different cancers and other benign, inflammatory pathologies, which may give rise to cross-reactions and loss of the specificity and sensitivity of the predictive assay. The extraordinary sensitivity of the immune system to detect minor alterations in self-proteins might be used to highlight changes in the cancer protein sequence and structure that can be used for personalized therapy, including immunotherapeutic vaccines. The increasing detection of kinase proteins as autoantibody targets points to new molecules with potential therapeutic impact


  1. 1.
    Anderson KS, LaBaer J. The sentinel within: exploiting the immune system for cancer biomarkers. J Proteome Res 2005 Jul–Aug; 4(4): 1123–33PubMedCrossRefGoogle Scholar
  2. 2.
    Shiku H, Takahashi T, Resnick LA, et al. Cell surface antigens of human malignant melanoma: III. Recognition of autoantibodies with unusual characteristics. J Exp Med 1977 Mar 1; 145(3): 784–9PubMedCrossRefGoogle Scholar
  3. 3.
    Chatterjee M, Mohapatra S, Ionan A, et al. Diagnostic markers of ovarian cancer by high-throughput antigen cloning and detection on arrays. Cancer Res 2006 Jan 15; 66(2): 1181–90PubMedCrossRefGoogle Scholar
  4. 4.
    Hudson ME, Pozdnyakova I, Haines K, et al. Identification of differentially expressed proteins in ovarian cancer using high-density protein microarrays. Proc Natl Acad Sci U S A 2007 Oct 30; 104(44): 17494–9PubMedCrossRefGoogle Scholar
  5. 5.
    Anderson KS, Ramachandran N, Wong J, et al. Application of protein microarrays for multiplexed detection of antibodies to tumor antigens in breast cancer. J Proteome Res 2008 Apr; 7(4): 1490–9PubMedCrossRefGoogle Scholar
  6. 6.
    Babel I, Barderas R, Diaz-Uriarte R, et al. Identification of tumor-associated autoantigens for the diagnosis of colorectal cancer in serum using high density protein microarrays. Mol Cell Proteomics 2009 Oct; 8(10): 2382–95PubMedCrossRefGoogle Scholar
  7. 7.
    Bouwman K, Qiu J, Zhou H, et al. Microarrays of tumor cell derived proteins uncover a distinct pattern of prostate cancer serum immunoreactivity. Proteomics 2003 Nov; 3(11): 2200–7PubMedCrossRefGoogle Scholar
  8. 8.
    Bradford TJ, Wang X, Chinnaiyan AM. Cancer immunomics: using autoantibody signatures in the early detection of prostate cancer. Urol Oncol 2006 May–Jun; 24(3): 237–42PubMedCrossRefGoogle Scholar
  9. 9.
    Wang X, Yu J, Sreekumar A, et al. Autoantibody signatures in prostate cancer. N Engl J Med 2005 Sep 22; 353(12): 1224–35PubMedCrossRefGoogle Scholar
  10. 10.
    Sahin U, Tureci O, Schmitt H, et al. Human neoplasms elicit multiple specific immune responses in the autologous host. Proc Natl Acad Sci U S A 1995 Dec 5; 92(25): 11810–3PubMedCrossRefGoogle Scholar
  11. 11.
    Chen YT, Scanlan MJ, Sahin U, et al. A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening. Proc Natl Acad Sci U S A 1997 Mar 4; 94(5): 1914–8PubMedCrossRefGoogle Scholar
  12. 12.
    Jongeneel V. Towards a cancer immunome database. Cancer Immun 2001 Mar 30; 1: 3Google Scholar
  13. 13.
    Klade CS, Voss T, Krystek E, et al. Identification of tumor antigens in renal cell carcinoma by serological proteome analysis. Proteomics 2001 Jul; 1(7): 890–8PubMedCrossRefGoogle Scholar
  14. 14.
    Hong SH, Misek DE, Wang H, et al. An autoantibody-mediated immune response to calreticulin isoforms in pancreatic cancer. Cancer Res 2004 Aug 1; 64(15): 5504–10PubMedCrossRefGoogle Scholar
  15. 15.
    Chen G, Gharib TG, Huang CC, et al. Proteomic analysis of lung adenocarcinoma: identification of a highly expressed set of proteins in tumors. Clin Cancer Res 2002 Jul; 8(7): 2298–305PubMedGoogle Scholar
  16. 16.
    Lueking A, Horn M, Eickhoff H, et al. Protein microarrays for gene expression and antibody screening. Anal Biochem 1999 May 15; 270(1): 103–11PubMedCrossRefGoogle Scholar
  17. 17.
    Qiu J, Madoz-Gurpide J, Misek DE, et al. Development of natural protein microarrays for diagnosing cancer based on an antibody response to tumor antigens. J Proteome Res 2004 Mar–Apr; 3(2): 261–7PubMedCrossRefGoogle Scholar
  18. 18.
    Zhong L, Hidalgo GE, Stromberg AJ, et al. Using protein microarray as a diagnostic assay for non-small cell lung cancer. Am J Respir Crit Care Med 2005 Nov 15; 172(10): 1308–14PubMedCrossRefGoogle Scholar
  19. 19.
    Mintz PJ, Kim J, Do KA, et al. Fingerprinting the circulating repertoire of antibodies from cancer patients. Nat Biotechnol 2003 Jan; 21(1): 57–63PubMedCrossRefGoogle Scholar
  20. 20.
    Bussow K, Nordhoff E, Lubbert C, et al. A human cDNA library for high-throughput protein expression screening. Genomics 2000 Apr 1; 65(1): 1–8PubMedCrossRefGoogle Scholar
  21. 21.
    Ramachandran N, Hainsworth E, Bhullar B, et al. Self-assembling protein microarrays. Science 2004 Jul 2; 305(5680): 86–90PubMedCrossRefGoogle Scholar
  22. 22.
    Ramachandran N, Raphael JV, Hainsworth E, et al. Next-generation high-density self-assembling functional protein arrays. Nat Methods 2008 Jun; 5(6): 535–8PubMedCrossRefGoogle Scholar
  23. 23.
    Tan EM, Zhang J. Autoantibodies to tumor-associated antigens: reporters from the immune system. Immunol Rev 2008 Apr; 222: 328–40PubMedCrossRefGoogle Scholar
  24. 24.
    DeLeo AB, Jay G, Appella E, et al. Detection of a transformation-related antigen in chemically induced sarcomas and other transformed cells of the mouse. Proc Natl Acad Sci U S A 1979 May; 76(5): 2420–4PubMedCrossRefGoogle Scholar
  25. 25.
    Anderson KS, Wong J, Vitonis A, et al. p53 autoantibodies as potential detection and prognostic biomarkers in serous ovarian cancer. Cancer Epidemiol Biomarkers Prev 2010 Mar; 19(3): 859–68PubMedCrossRefGoogle Scholar
  26. 26.
    Chen G, Wang X, Yu J, et al. Autoantibody profiles reveal ubiquilin 1 as a humoral immune response target in lung adenocarcinoma. Cancer Res 2007 Apr 1; 67(7): 3461–7PubMedCrossRefGoogle Scholar
  27. 27.
    Qiu J, Choi G, Li L, et al. Occurrence of autoantibodies to annexin I, 14-3-3 theta and LAMR1 in prediagnostic lung cancer sera. J Clin Oncol 2008 Nov 1; 26(31): 5060–6PubMedCrossRefGoogle Scholar
  28. 28.
    Koziol JA, Zhang JY, Casiano CA, et al. Recursive partitioning as an approach to selection of immune markers for tumor diagnosis. Clin Cancer Res 2003 Nov 1; 9(14): 5120–6PubMedGoogle Scholar
  29. 29.
    Taylor BS, Pal M, Yu J, et al. Humoral response profiling reveals pathways to prostate cancer progression. Mol Cell Proteomics 2008 Mar; 7(3): 600–11PubMedGoogle Scholar
  30. 30.
    Gnjatic S, Ritter E, Buchler MW, et al. Seromic profiling of ovarian and pancreatic cancer. Proc Natl Acad Sci U S A 2010 Mar 16; 107(11): 5088–93PubMedCrossRefGoogle Scholar
  31. 31.
    Scanlan MJ, Welt S, Gordon CM, et al. Cancer-related serological recognition of human colon cancer: identification of potential diagnostic and immunotherapeutic targets. Cancer Res 2002 Jul 15; 62(14): 4041–7PubMedGoogle Scholar
  32. 32.
    Zhang JY, Casiano CA, Peng XX, et al. Enhancement of antibody detection in cancer using panel of recombinant tumor-associated antigens. Cancer Epidemiol Biomarkers Prev 2003 Feb; 12(2): 136–43PubMedGoogle Scholar
  33. 33.
    Bei R, Masuelli L, Palumbo C, et al. A common repertoire of autoantibodies is shared by cancer and autoimmune disease patients: inflammation in their induction and impact on tumor growth. Cancer Lett 2009 Aug 18; 281(1): 8–23PubMedCrossRefGoogle Scholar
  34. 34.
    Segal NH, Parsons DW, Peggs KS, et al. Epitope landscape in breast and colorectal cancer. Cancer Res 2008 Feb 1; 68(3): 889–92PubMedCrossRefGoogle Scholar
  35. 35.
    Chatterjee M, Draghici S, Tainsky MA. Immunotheranostics: breaking tolerance in immunotherapy using tumor autoantigens identified on protein microarrays. Curr Opin Drug Discov Devel 2006 May; 9(3): 380–5PubMedGoogle Scholar

Copyright information

© Adis Data Information BV 2010

Authors and Affiliations

  1. 1.Functional Proteomics Laboratory, Centro de Investigaciones BiológicasConsejo Superior de Investigaciones Científicas (CIB-CSIC)MadridSpain

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